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Through the 1800s, Wyoming would primarily remain an agricultural location and its development occurred near transportation routes in the region. The area that is now the city of Wyoming was the second location settled by European-Americans in Kent County. Robert Howlett, Luther Lincoln Amos Gordon and Stephen Tucker were some of the first settlers in the fall of 1832 with many settling near Buck Creek. Lincoln built the first log shanty in the area in the fall of 1832 while Tucker and Native Americans constructed the first established house for his family in March 1833. The first settlers had a successful harvest, constructing gristmills and sawmills on Buck Creek a year later in 1833. In late 1835, the first wedding occurred with Sylvester Hills and Harriet Burton.

The town was first organized as Byron Township on May 2, 1836 and was headquartered at the home of Charles H. Oakes in what is now the city of Grandville. It was this year that one of Wyoming's most notable pioneers, Justice C. Rogers, established his homestead on what is now the southwest corner of 28th Street and Clyde Park Avenue.

The following year in 1837, the launch of the pole boat propelled by a quant, the Cinderella, was celebrated as a major development for the town. A framed house Rogers constructed in the spring of 1836 and was destroyed by a tornado in September 1836. Rogers Mansion was then constructed with the second story being finished in 1839.

On April 3, 1848 the 72 square miles (190 km²) township of Byron divided in half during , with the name of Wyoming being used for the northern 36 square miles (93 km²) portion where the majority of the population was settled. with many settling near Buck Creek. At the time of division, about 500 people lived in Wyoming while a little less than 200 lived in Byron. The name came from the Wyoming County, New York from which the majority of the residents came during the first 16 years. Two years later in 1850, the population of Wyoming Township was counted at 543 people.

In 1870 a settlement known as Fisher's Station developed around a station on the Grand Rapids and Indiana Railroad. A post office was constructed in 1871 and the area was platted in December 1873. The population of Wyoming Township grew to 2,008 in 1874 while the population of Fisher's Station was 65 in 1888.

Wyoming began to grow as a suburb of Grand Rapids in 1890 with the city's next major area of development occurring in the northeast section of the township with much of the city's population moving southward in the early 1900s. The City of Grand Rapids started annexing portions of the township and by 1891 had annexed one square mile (2.6 km²) of the city from Division to Clyde Park and from Hall to Burton. In 1902, the Grand Rapids, Holland and Chicago Railway promoted the creation of more plats in the Galewood, Urbandale and Burlingame (GUB) neighborhoods, with the railway providing transportation to downtown Grand Rapids in fifteen minutes. From 1890 to 1906, thirty-two plats were in the GUB neighborhoods. Another section of Wyoming was annexed by Grand Rapids in 1916 that involved half-mile from Burton to Alger and from Clyde Park to Division. Following the end of World War I in 1918, there was a large increase in the platting of residential properties, especially the neighborhoods of Godwin Heights, Home Acres and Wyoming Park, with plat proposals occurring during every town meeting at the time.

With Wyoming developing at such a rapid pace, the Grand Rapids city officials and affiliated business leaders attempted to deter the development of industry in Wyoming, fearing that Grand Rapids would lose skilled workers and wages would increase. One major incident of Grand Rapids preventing industrial development in Wyoming occurred in the early-1920s when Ford Motor Company attempted to purchase an unfinished picric acid on the west side of 44th Street and Clyde Park Avenue that was being constructed during World War I. Kendall Furniture quickly purchased the property before Ford could acquire the site, later selling the property for tax purposes.

As a result of suburbanization the population of Wyoming had increased over 250% between 1920 and 1930, from 6,501 to 16,931.

As the Great Depression affected the world's economy in the 1930s, Grand Rapids saw little industrial development as there was no demand for furniture, the city's main economic product. During the economic depression, at least twenty-five percent of Wyoming residents were unemployed. Former Mayor of Grand Rapids George P. Tilma was elected supervisor of Wyoming Township in 1932 and was tasked with modernizing the developing suburban community from a rural town system.

General Motors sought to construct a new facility in Grand Rapids, though there were no areas for development or future expansions, so the cities of Grand Rapids and Wyoming collaborated to have General Motors purchase land in Wyoming while Grand Rapids supplied utilities to the site. Tilma's expertise was instrumental in both secretly negotiating with Grand Rapids on utility work and with obtaining approval of the site by General Motors. The General Motors plant began construction on January 22, 1936 and the first metal stamps were shipped from the factory on June 1, 1936. The first enrollment date for employees on April 6, 1936 saw a line of workers spanning nearly 1.5 miles (2.4 km) from the factory's entrance west of Buchanan Avenue and 36th Street, east to Division Avenue and then north 1 mile (1.6 km) to 28th Street.

Following the construction of the General Motors stamping plant, development on Division Avenue increased extensively, with a new Kelloggsville High School being opened in September 1936 and a new Godwin Heights High School being approved in January 1937. Supervisor Tilma died suddenly in his office in April 1937 with his death being attributed to an intracerebral hemorrhage. As World War II began, Reynolds Metals opened a plant in the township that was initially to develop airplane material in 1942.

Following World War II, Wyoming developed so rapidly that mobile homes began to appear on vacant properties throughout the city, with an ordinance being passed in 1947 to prevent this.

As Wyoming moved towards cityhood, the township purchased 5 acres (20,000 m²) of land from Judy Devine in December 1947 on the northeast corner of 28th Street and DeHoop Avenue, establishing the area as the town center of Wyoming due to the increased development on 28th Street. A year later in 1948, Lake Alexander was drained and converted into what is now Jackson Park. In May 1948, a committee was created by the township which recommended incorporating Wyoming into a city. As Wyoming pursued incorporation, Grand Rapids increased annexation attempts, with the annexation of GUB being defeated in April 1949.

The 1950s was the decade of Wyoming's fastest development, with homes developing so quickly that the township experienced difficulties providing proper utilities to homes. Multiple wells were drilled throughout the area to provide water to the developing community after the water supply from Grand Rapids was discontinued, temporarily sparking political controversy surrounding water supplies. The township board approved of a route for U.S. Route 131 through Wyoming in July 1952 and 28th Street was widened from two to four lanes shortly after. In August 1956, a vote for incorporation into a city was narrowly defeated and the Ivanrest area was annexed by Grandville. Rogers Department Store, one of the largest department stores in Michigan at the time, opened on 28th Street in 1955. On November 6, 1958, voters approved the incorporation of Wyoming into a city.

In the 1960s, the city was able to launch several projects. The first was a sewage plant to take care of issues from the state in regards to dumping it in the Buck Creek and Grand River. The next was the completion of the Water Plant in Holland with a pipeline to the city.

New developments occurred over the decade on 28th Street, with free vehicle parking drawing some shoppers away from Grand Rapids. One major project was Rogers Plaza, which opened in August 1961 as the first indoor shopping mall in Michigan and one of the first in the United States, including stores such as S. S. Kresge, W. T. Grant, Kroger, A&P, Cunningham Drug and Montgomery Ward. The neighboring Wyoming Village Mall opened later in 1961 and was anchored by Wurzburg's. Flowerland Fruitbasket also opened in 1961 providing lawn care tools, flowers and outdoor furniture for the developing suburban homes.Gordon Food Service moved from Grand Rapids to Wyoming in 1962. Three annexation attempts by Grand Rapids were also defeated in that year; the Kent County Airport, the Blackburn neighborhood and Buchanan neighborhood.Studio 28 opened on the 28th Street corridor in 1965 and expanded in size over decades into the world's first multiplex and the largest multiplex in the world in 1988. In July 1966, the Lake Michigan pipeline to Wyoming began to supply water to the city, a major accomplishment after years of difficulties with low-quality wells. By the end of the decade, the city faced fund shortages and multiple income tax proposals were turned down. Wyoming began to establish many municipal facilities in the 1970s, including a public works building, a centralized fire station, a combined Police-Justice building and a new public library.

By the 1980s, the city became concerned about the quality of developments, with adult bookstores and massage parlors appearing. In 1990, Reynolds Metals closed their operations in the city. Following the 1999 opening of Rivertown Crossings Mall in Grandville near the southwest border of Wyoming, many commercial tenants left the 28th Street corridor. The once-popular Rogers Department Store closed in 2003. More business was lost in the late-2000s into the 2010s during the great recession, with the GM Fisher Body Plant closed due to budget cuts by General Motors. Much of the commercial atmosphere of 28th Street also dwindled down, with Studio 28 closing in 2008 and vacancy rates up to nearly 40% in 2011.

In the mid-2010s, development spread to southern Wyoming. Gordon Foods expanded its headquarters in 2012 and development occurred near the recently built Metro Health Hospital. The 28 West plan was also initiated to make 28th Street a more pedestrian-friendly corridor while also centralizing the development of food, retail and entertainment projects in the city's center, effectively creating a downtown area.

As of the census of 2010, there were 72,125 people, 26,970 households, and 18,128 families residing in the city. The population density was 2,927.2 inhabitants per square mile (1,130.2/km²). There were 28,983 housing units at an average density of 1,176.3 per square mile (454.2/km²). The racial makeup of the city was 75.8% White, 7.2% African American, 0.6% Native American, 2.8% Asian, 9.6% from other races, and 3.8% from two or more races. Hispanic or Latino of any race were 19.4% of the population.

There were 26,970 households, of which 37.2% had children under the age of 18 living with them, 47.1% were married couples living together, 14.4% had a female householder with no husband present, 5.7% had a male householder with no wife present, and 32.8% were non-families. 25.6% of all households were made up of individuals, and 7.3% had someone living alone who was 65 years of age or older. The average household size was 2.66 and the average family size was 3.22.

The median age in the city was 32.1 years. 27.1% of residents were under the age of 18; 10.5% were between the ages of 18 and 24; 29.9% were from 25 to 44; 23.5% were from 45 to 64; and 9% were 65 years of age or older. The gender makeup of the city was 49.3% male and 50.7% female.

As of the census of 2000, there were 69,368 people, 26,536 households, and 17,540 families residing in the city. The population density was 2,840.1 per square mile (1,096.8/km²). There were 27,506 housing units at an average density of 1,126.2 per square mile (434.9/km²). The racial makeup of the city was 84.32% White, 4.85% African American, 0.59% Native American, 2.92% Asian, 0.04% Pacific Islander, 4.70% from other races, and 2.59% from two or more races. Hispanic or Latino of any race were 9.66% of the population.

There were 26,536 households, out of which 35.7% had children under the age of 18 living with them, 49.6% were married couples living together, 12.0% had a female householder with no husband present, and 33.9% were non-families. 26.6% of all households were made up of individuals, and 7.4% had someone living alone who was 65 years of age or older. The average household size was 2.60 and the average family size was 3.19.

In the city, the population was spread out, with 28.0% under the age of 18, 10.9% from 18 to 24, 33.7% from 25 to 44, 18.0% from 45 to 64, and 9.4% who were 65 years of age or older. The median age was 31 years. For every 100 females, there were 97.5 males. For every 100 females age 18 and over, there were 95.0 males.

The median income for a household in the city was $43,164, and the median income for a family was $50,002. Males had a median income of $35,772 versus $25,482 for females. The per capita income for the city was $19,287. About 5.1% of families and 7.3% of the population were below the poverty line, including 8.8% of those under age 18 and 6.9% of those age 65 or over.

Christian Reformed Dutch settlers established the first churches in Wyoming, with Grandville Avenue Christian Reformed Church being founded in 1891, with the church now being part of The Potter's House school. Holy Name of Jesus Catholic Church was created in 1908, serving as the place of worship for Roman Catholics in Wyoming. The episcopal population established the Holy Trinity Episcopal Church at an old chicken coop in 1957. The Assemblies of God established a church in 1929 and moved to their current location on 44th Street in 1977, with the facility being able to seat 1,400 people.