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In 1638, the Dutch West India Company secured a deed from the local Lenape people for the Bushwick area, and Peter Stuyvesant chartered the area in 1661, naming it Boswijck, meaning "neighborhood in the woods" in 17th-century Dutch. Its area included the modern-day communities of Bushwick, Williamsburg, and Greenpoint. Bushwick was the last of the original six Dutch towns of Brooklyn to be established within New Netherland.

The community was settled, though unchartered, on February 16, 1660, on a plot of land between the Bushwick and Newtown Creeks by fourteen French and Huguenot settlers, a Dutch translator named Peter Jan De Witt, and one of the original eleven slaves brought to New Netherland, Franciscus the Negro, who had worked his way to freedom. The group centered their settlement on a church located near today's Bushwick and Metropolitan Avenues. The major thoroughfare was Woodpoint Road, which allowed farmers to bring their goods to the town dock. This original settlement came to be known as Het Dorp by the Dutch, and, later, Bushwick Green by the British. The English would take over the six towns three years later and unite them under Kings County in 1683.

Many of Bushwick's Dutch records were lost after its annexation by Brooklyn in 1854. Contemporary reports differ on the reason: T. W. Field writes that "a nice functionary of the [Brooklyn] City Hall ... contemptuously thrust them into his waste-paper sacks", while Eugene Armbruster claims that the movable bookcase containing the records "was coveted by some municipal officer, who turned its contents upon the floor".

At the turn of the 19th century, Bushwick consisted of four villages: Green Point, Bushwick Shore (later known as Williamsburg), Bushwick Green, and Bushwick Crossroads (at the spot where today's Bushwick Avenue turns southeast at Flushing Avenue).

Bushwick's first major expansion occurred after it annexed the New Lots of Bushwick, a hilly upland originally claimed by Native Americans in the first treaties they signed with European colonists granting the settlers rights to the lowland on the water. After the second war between the natives and the settlers broke out, the natives fled, leaving the area to be divided among the six towns in Kings County. Bushwick had the prime location to absorb its new tract of land in a contiguous fashion. New Bushwick Lane (Evergreen Avenue), a former Native American trail, was a key thoroughfare for accessing this new tract, which was suitable mostly for potato and cabbage agriculture. This area is bounded roughly by Flushing Avenue to the north and Evergreen Cemetery to the south. In the 1850s, the New Lots of Bushwick area began to develop. References to the town of Bowronville, a new neighborhood contained within the area south of Lafayette Avenue and Stanhope Street, began to appear in the 1850s.

The area known as Bushwick Shore was so called for about 140 years. Bushwick residents called Bushwick Shore "the Strand", another term for "beach". Bushwick Creek, in the north, and Cripplebush, a region of thick, boggy shrubland extending from Wallabout Creek to Newtown Creek, in the south and east, cut Bushwick Shore off from the other villages in Bushwick. Farmers and gardeners from the other Bushwick villages sent their goods to Bushwick Shore to be ferried to New York City for sale at a market located at the present-day Grand Street. Bushwick Shore's favorable location close to New York City led to the creation of several farming developments. Originally a 13-acre (53,000 m²) development within Bushwick Shore, Williamsburgh rapidly expanded during the first half of the 19th century and eventually seceded from Bushwick to form its own independent city in 1852. Both Bushwick and Williamsburgh were annexed to the City of Brooklyn in 1854.

When Bushwick was founded, it was primarily an area for farming food and tobacco. As Brooklyn and New York City grew, factories that manufactured sugar, oil, and chemicals were built. The inventor Peter Cooper built a glue manufacturing plant, his first factory, in Bushwick. Immigrants from western Europe joined the original Dutch settlers. The Bushwick Chemical Works, at Metropolitan Avenue and Grand Street on the English Kills channel, was another early industry among the lime, plaster, and brickworks, coal yards, and other factories that developed along English Kills, which was dredged and made an important commercial waterway. In October 1867, the American Institute awarded Bushwick Chemical Works the first premium for commercial acids of the greatest purity and strength. The Bushwick Glass Company, later known as Brookfield Glass Company, established itself in 1869, when a local brewer sold it to James Brookfield. It made a variety of bottles and jars, as well as large numbers of glass electrical insulators for telegraph, telephone and power lines.

In the 1840s and 1850s, a majority of the immigrants were German, which became the dominant population. Bushwick established a considerable brewery industry, including "Brewer's Row"—14 breweries operating in a 14-block area—by 1890. Thus, Bushwick was dubbed the "beer capital of the Northeast". The last Bushwick breweries, the Schaefer's and Rheingold Breweries, closed its doors in 1976. As late as the 1980s, there were unsuccessful efforts to revive the Rheingold Brewery. The William Ulmer Brewery at Beaver and Belvidere Streets was given landmark status by the city in 2010, becoming the first brewery with such a status.

As late as 1883, Bushwick maintained open farming land east of Flushing Avenue. A synergy developed between the brewers and the farmers during this period, as the dairy farmers collected spent grain and hops for cow feed. The dairy farmers sold milk and other dairy products to consumers in Brooklyn. Both industries supported blacksmiths, wheelwrights, and feed stores along Flushing Avenue.

In 1868, the Long Island Rail Road built the Bushwick Branch from its hub in Jamaica via Maspeth to Bushwick Terminal, at the intersection of Montrose and Bushwick avenues, allowing easy movement of passengers, raw materials, and finished goods. Routes also radiated to Flushing, Queens.

The first elevated railway ("el") in Brooklyn, known as the Lexington Avenue Elevated, opened in 1885. Its eastern terminus was at the edge of Bushwick, at Gates Avenue and Broadway. This line was extended southeastward into East New York shortly thereafter. By the end of 1889, the Broadway Elevated and the Myrtle Avenue Elevated were completed, enabling easier access to Downtown Brooklyn and Manhattan and the rapid residential development of Bushwick from farmland.

With the success of the brewing industry and the presence of the els, another wave of European immigrants settled in the neighborhood. Also, parts of Bushwick became affluent. Brewery owners and doctors commissioned mansions along Bushwick and Irving Avenues at the turn of the 20th century. New York mayor John Francis Hylan kept a townhouse on Bushwick Avenue during this period. Bushwick homes were designed in the Italianate, Neo Greco, Romanesque Revival, and Queen Anne styles by well-known architects. Bushwick was a center of culture, with several Vaudeville-era playhouses, including the Amphion Theatre, the nation's first theatre with electric lighting. The wealth of the neighborhood peaked between World War I and World War II, even when events such as Prohibition and the Great Depression were taking place. After World War I, the German enclave was steadily replaced by a significant proportion of Italian Americans. By 1950, Bushwick was one of New York City's largest Italian American neighborhoods, although some German Americans remained.

The Italian community was composed almost entirely of Sicilians, mostly from the Palermo, Trapani, and Agrigento provinces in Sicily. In particular, the Sicilian townsfolk of Menfi, Santa Margherita di Belice, Trapani, Castelvetrano, and many other paesi had their own clubs (clubbu) in the area. Il Circolo di Santa Margherita di Belice, founded in Bushwick, remains the oldest operating Sicilian organization in the United States. These clubs often started as mutual benevolence associations or funeral societies but transformed along with the needs of their communities from the late 1800s until the 1960s, when many began to fade away. St. Joseph Patron of the Universal Church Roman Catholic Parish was the hub of the Sicilian community, and held five feasts during the year, complete with processions of saints or Our Lady of Trapani. St. Joseph opened in 1923 because the Italian community had been rapidly growing in Bushwick since 1900. This Sicilian community first was centered in Our Lady of Pompeii parish on Siegel Street in Williamsburgh. But as industry expanded along Flushing Avenue, the Sicilian population expanded with the growing need for labor by factory operators. St. Leonard's parish was the large German Catholic parish in the area, but the Italian community was not welcome there and was thus compelled to open its own parish. St. Leonard's closed in 1973. St. Joseph's is now a large and vibrant Latino parish run by the Scalabrini Order of priests, an Italian missionary order that caters to migrants.

The demographic transition of Bushwick after World War II was similar to that of many Brooklyn neighborhoods. The U.S. Census records show that the neighborhood's population was almost 90% white in 1960, but dropped to less than 40% white by 1970. During this transition, white-collar workers were being replaced by those migrating from the south. Puerto Ricans and African Americans, among other Caribbean American families, moved into homes in the southeastern edge of the neighborhood, closest to Eastern Parkway. By the mid-1950s, migrants began settling into central Bushwick. The availability of block association housing helped many neighborhoods survive the economic and social distress of the 1970s.

This change in demographics coincided with changes in the local economy. Rising energy costs, advances in transportation and the change to the use of aluminum cans encouraged beer companies to move out of New York City. As breweries in Bushwick closed, the neighborhood's economic base eroded. Discussions of urban renewal took place in the 1960s, but never materialized, resulting in the demolition of many residential buildings with the intent of replacing these structures with public housing, but nothing new was built in its place as these proposals were scrapped. Another contribution to the change in the socioeconomic profile of the neighborhood was the John Lindsay administration's policy of raising available rent for welfare recipients. Since these tenants could now bring higher rents than tenants would on the open market, landlords began filling vacant units with such tenants. By the mid-1970s, half of Bushwick's residents were on public assistance.

According to The New York Times, Bushwick was "a neatly maintained community of wood houses" by the mid-1960s. Within five years, it had become "what often approached a no man's land of abandoned buildings, empty lots, drugs and arson."

On the night of July 13, 1977, a major blackout cut power to nearly all of New York City, and arson, looting, and vandalism occurred in low-income neighborhoods across the city. Bushwick suffered some of the most devastating damage and losses. While store owners along Knickerbocker and Graham avenues were able to defend their stores, the Broadway shopping district was heavily looted and burned. Twenty-seven stores along Broadway were burned, and looters and some residents saw the blackout as an opportunity to get what they otherwise could not afford.^:104 Newspapers around the country published UPI and the Associated Press's photos of Bushwick residents with stolen items and a police officer beating a suspected looter, and Bushwick became known for riots and looting. Fires spread to many residential buildings as well. After the riots were over and the fires were put out, residents saw unsafe dwellings and empty lots among surviving buildings, leading one author to describe the scene as "some streets that looked like Brooklyn Heights, and others that looked like Dresden in 1945": The business vacancy rate on Broadway reached 43% in the wake of the riots.

The 1977 blackout and resulting riots left Bushwick without a commercial retail hub. Middle-class residents who could afford to leave did so, in some cases abandoning their homes. New immigrants continued to move to the area, many from Hispanic America, but renovation and new construction was outpaced by the demolition of unsafe buildings, forcing overcrowded conditions at first. As buildings came down, the vacant lots made parts of the neighborhood look and feel desolate, resulting in a greater outflow of residents and a growth of the illegal drug trade due to a lack of job opportunities. Author Jonathan Mahler described the social and economic hardships of Bushwick after the blackout in his book Ladies and Gentlemen, the Bronx is Burning, explaining that the majority of neighborhood residents were living on less than $4,000 a year, and had to rely on some form of public assistance. By the 1980s, the Knickerbocker Avenue shopping district was nicknamed "The Well" for its seemingly unending supply of drugs. Even through the 1990s, it remained a poor and relatively dangerous area, with 77 murders, 80 rapes, and 2,242 robberies in 1990.

Since 2000, the rise of real estate prices in nearby Manhattan has made the neighborhood more attractive to younger professionals. In the wake of reduced crime rates citywide and a shortage of affordable housing in nearby neighborhoods such as Park Slope and Williamsburg, numerous young professionals and artists have moved into converted warehouse lofts, brownstones, limestone-brick townhouses, and other renovated buildings in Bushwick.

A flourishing artist community has existed in Bushwick for decades and has become more visible in the neighborhood. Dozens of art studios and galleries are scattered throughout the neighborhood. Several open studios programs are conducted that enable the public to visit artist studios and galleries, and several websites are devoted to promoting neighborhood art and events. Bushwick artists display their works in galleries and private spaces throughout the neighborhood. The borough's first and only trailer park, a 20-person art collective established by founder, Hayden Cummings and ZenoRadio's Baruch Herzfeld, was established within a former nut roasting factory for live/work spaces.A Bushwick-centered news site, entitled Bushwick Daily, was founded in 2009, and features community issues, events, food, art and culture.

Starting in the mid-2000s, the city and state governments began the Bushwick Initiative, a two-year pilot program spearheaded by the New York City Department of Housing Preservation and Development (HPD) and various community projects. The group's goal was to improve quality of life in the twenty-three square blocks surrounding Maria Hernandez Park through various programs such as addressing deteriorated housing conditions, increasing economic development opportunities, and reducing drug dealing activities. The group's crime-reduction activities included collaboration with the HPD's Narcotics Control Unit and the New York City Police Department's 83rd Precinct and Narcotics Division to reduce drug-dealing. In addition, to reduce lead hazards in buildings, HPD and DOHMH created a grant program focusing on residential buildings in the initiative's coverage area, which resulted in fines for dozens of landlords with lead paint hazards. The Bushwick Initiative's economic development efforts were also focused on revitalizing the Knickerbocker Avenue commercial district, and adding a thousand rat-resistant public trash cans to reduce litter.

In 2019, the New York City Department of City Planning released a Bushwick rezoning plan covering 300 city blocks. The plan would allow for high-density development on Broadway and Myrtle and Wyckoff Avenues.

The entirety of Community Board 4 had 112,388 inhabitants as of NYC Health's 2018 Community Health Profile, with an average life expectancy of 80.4 years.^{:2, 20} This is lower than the median life expectancy of 81.2 for all New York City neighborhoods.^{:53 (PDF p. 84)} Most inhabitants are middle-aged adults and youth: 24% are between the ages of 0–17, 35% between 25 and 44, and 20% between 45 and 64. The ratio of college-aged and elderly residents was lower, at 12% and 9% respectively.

As of 2016, the median household income in Community Board 4 was $50,656. In 2018, an estimated 25% of Bushwick residents lived in poverty, compared to 21% in all of Brooklyn and 20% in all of New York City. One in eight residents (13%) were unemployed, compared to 9% in the rest of both Brooklyn and New York City. Rent burden, or the percentage of residents who have difficulty paying their rent, is 55% in Bushwick, higher than the citywide and boroughwide rates of 52% and 51% respectively. Based on this calculation, as of 2018, Bushwick is considered to be gentrifying.^:7

Though an ethnic neighborhood, Bushwick's population is, for a New York City neighborhood, relatively heterogeneous, scoring a 0.5 on the Furman Center's racial diversity index, making it the city's 35th most diverse neighborhood in 2007. Most residents are Latino American citizens from the island of Puerto Rico and immigrants from the Dominican Republic. Since the turn of the 21st century, the population of native-born Americans has increased, as have other Latino groups, particularly immigrants from Mexico and El Salvador. In 2008 the neighborhood's median household income was $28,802. 32% of the population falls under the poverty line, making Bushwick the 7th-most impoverished neighborhood in New York City. More than 75% of children in the neighborhood are born in poverty. Some 40.3% of students in Bushwick read at grade level in 2007, making it the 49th most literate neighborhood in the city that year. 58.2% of students could work math at grade level in Bushwick, and it ranked as 41st in the city.

Bushwick is the most populous Hispanic-American community in Brooklyn, although Sunset Park also has a large Hispanic population. As in other neighborhoods in New York City, Bushwick's Hispanic population is mainly from Puerto Rico and the Dominican Republic. It also has a sizable population from South American nations. As nearly 70% of Bushwick's population is Hispanic, residents have created many businesses to support their various national and distinct traditions in food and other items. The neighborhood's major commercial streets are Knickerbocker Avenue, Myrtle Avenue, Wyckoff Avenue, and Broadway.

There are two neighborhood tabulation areas that covered Bushwick as of the 2010 United States Census. The total population of these districts was 129,239.

Based on data from the 2010 United States Census, the population of Bushwick North was 57,138, an increase of 1,045 (1.9%) from the 56,093 counted in 2000. Covering an area of 570.78 acres (230.99 ha), the neighborhood had a population density of 100.1 inhabitants per acre (64,100/sq mi; 24,700/km²).

The ethnic and racial makeup of the neighborhood as of 2010 was 10.7% (6,098) non-Hispanic white, 9.7% (5,533) non-Hispanic black, 0.1% (82) Native American, 6.0% (3,417) Asian, 0.0% (11) Pacific Islander, 0.7% (380) from other races, and 1.0% (582) from two or more races. Hispanic or Latino of any race were 71.8% (41,035) of the population.

Based on data from the 2010 United States Census, the population of Bushwick South was 72,101, an increase of 7,484 (11.6%) from the 64,617 counted in 2000. Covering an area of 923.64 acres (373.78 ha), the neighborhood had a population density of 78.1 inhabitants per acre (50,000/sq mi; 19,300/km²).

The racial makeup of the neighborhood was 9.5% (6,819) non-Hispanic white, 28.1% (20,281) black, 0.2% (155) Native American, 2.4% (1,734) Asian, 0.0% (21) Pacific Islander, 0.4% (268) from other races, and 1.1% (809) from two or more races. Hispanic or Latino of any race were 58.3% (42,014) of the population.

Bushwick and neighboring East New York are the center for the Hispanic community in Brooklyn. In the post-World War II period, Bushwick was still a predominantly Irish and Italian-American community. Puerto Ricans began to migrate to New York for greater opportunities, developing Hispanic enclaves in Brooklyn, East Harlem, the Upper West Side, and the Bronx. Many Puerto Ricans also settled in neighboring Williamsburg, also known as Los Sures, due to the proximity to jobs at the now defunct Domino Sugar Refinery as well as at the Brooklyn Navy Yard; they expanded into other parts of Brooklyn as ethnic Irish and Italians moved to suburbs in Queens and Nassau County.

Salsa music, corner bodegas, and Latin cuisine are part of the cultural dynamic of the Bushwick community. The neighborhood contains the largest concentration of Hispanic Americans in the entire borough, followed closely behind by Sunset Park. The Williamsburg and Bushwick communities are home to their own local Puerto Rican Day Parade. The parade board usually meets at the Orocovis Social Club, located off Myrtle Avenue. La Isla Restaurant, located off Myrtle Avenue and Knickerbocker, is popular for its Puerto Rican and Dominican cuisine. On the corner of Broadway, Flushing Avenue and Graham Avenue, where Bushwick, Williamsburg and Bedford–Stuyvesant meet, in the shadow of Woodhull Medical Center, Graham Avenue becomes the Avenue of Puerto Rico.

A campus of Boricua College and a branch of the Puerto Rico-based Popular Community Bank are located within the Bushwick area. Make the Road New York, a Latino community group, has a chapter in the neighborhood. So important is the activism of local Latinos that in 2016, Democratic Party presidential candidate Bernie Sanders campaigned in Bushwick in order to reach Hispanic votes. A web show, East Willy B, was created to explore the struggles of the local Latino community.