The area that includes what became Scottsdale was originally inhabited by the Hohokam, from approximately 300 BC to 1450 AD. This ancient civilization farmed the area and developed a complex network of canals for irrigation that was unsurpassed in pre-Columbian North America. At its peak, the canals stretched over 250 miles. Many remain extant today, some having been renovated and put back into use in the 20th century. Under still-mysterious circumstances, the Hohokam disappeared around 1450 or 1500, most likely because of a prolonged drought. The area's later occupants, the Akimel O'odham (Pima) and the Tohono O'odham (Papago), are thought to be the Hohokam's direct descendants.

Before European settlement, Scottsdale was a Pima village known as Vaṣai S-vaṣonĭ, meaning "rotting hay." Some Pima remained in their original homes well into the 20th century. Until the late 1960s, there was a still-occupied traditional dwelling on the southeast corner of Indian Bend Road and Hayden Road. Pima who live in Scottsdale now reside in newer homes, not traditional dwellings. Many Pima and Maricopa people continue to reside on the Salt River Pima-Maricopa Indian Community, which borders Scottsdale to the south and east.

In the early to mid-1880s, U.S. Army Chaplain Winfield Scott visited the Salt River Valley and was impressed with it and its potential for agriculture. Returning in 1888 with his wife, Helen, he purchased 640 acres for $3.50 ($92 as of 2015) an acre for a stretch of land where downtown Scottsdale is now. Winfield and his brother George Washington Scott became the town's first residents. It was soon known as Orangedale due to the large citrus groves the Scotts planted. Many of the community's original settlers, recruited by Scott from the East and Midwest, were educated and had an appreciation for cultural activities. The town was renamed Scottsdale in 1894.

In 1896, these settlers established the Scottsdale Public School system, and opened the first schoolhouse, which was followed by the opening of the first general store by J. L. Davis, which also housed the first post office for Scottsdale in 1897. In the early 1900s the community supported an artists and writers culture, culminating in the opening of the region's first resort in 1909, the Ingleside Inn, just south of the Arizona Canal and west of the Crosscut Canal (Indian School Road at about 64th Street) in what is today Scottsdale. Also in 1909, Cavalliere's Blacksmith Shop opened in downtown Scottsdale, and the original schoolhouse was replaced by the much more expansive Little Red Schoolhouse, which stands to this day. While not in its original building, Cavalliere's has been in continuous operation since that time.

In 1912, both the Phoenix Street Railway Company and a competitor, the Salt River Valley Electric Railway Company, proposed building streetcar lines to Scottsdale but due to an economic downturn, neither was built.

Between 1908 and 1933, due to the construction of the Granite Reef and Roosevelt dams (in 1908 and 1911, respectively), Scottsdale's population experienced a boom, growing steadily during those years. It became a small market town providing services for families involved in the agricultural industry.

During the First World War Scottsdale and its environs supported a large cotton farming industry, due to the creation of Long Staple Egyptian Cotton, developed by the US Department of Agriculture. Cotton is still grown in southern Arizona, but Scottsdale's cotton boom ended with the loss of government contracts at the end of the war.

In 1920, a second resort was opened on 12 acres of property owned by the artist Jessie Benton Evans. Called the Jokake Inn, meaning "mud house," the structure still stands on the grounds of the Phoenician Resort.

The Depression years saw an influx of artists and architects to Scottsdale, which included, in 1937, Frank Lloyd Wright. Wright and his wife purchased 600 desert acres at the foot of the McDowell Mountains and established Taliesin West, his winter home and his architectural firm's southwestern headquarters. Scottsdale and the rest of Phoenix have seen an everlasting influence from Wright. Many buildings throughout the region were designed by him. His influence on the regional architecture is commemorated by a major street bearing his name and a 125-foot (38 m) spire memorial designed by Wright in North Scottsdale.

Among the more significant events during the years of World War II was the opening of Thunderbird II Airfield in 1942 (which later became Scottsdale Airport), where 5,500 pilot cadets received their primary flight training before the war's end. Scottsdale was the site of a German POW camp at the intersection of Scottsdale and Thomas Roads in what today is Papago Park.

In 1950, the town continued to grow as Motorola became the first of many technology companies to build a plant in Scottsdale. It built a second plant in 1956. With a population of approximately 2,000, the city was incorporated on June 25, 1951. It appointed its first mayor, Malcolm White, and adopted the motto "The West's Most Western Town." The seal, depicting a mounted cowboy surrounded by a 64-pointed starburst, was designed by Mrs. Gene Brown Pennington. The city also became a tourist destination with the opening of the city's first modern resorts, the Hotel Valley Ho and the Safari Hotel, in 1956.

The town began a period of rapid population growth after its incorporation in 1951, growing from 2,000 to 10,000 residents during the 1950s. This growth necessitated development into the flood plain known as the Indian Bend Wash. Flood plains throughout history have been enticing locations for development due to their flatness, ease of building and inexpensiveness. This is even more tempting in a desert, where flooding so rarely happens. As Scottsdale expanded, the Indian Bend Wash virtually bisected the city in half north to south. In the late 1950s, the problem became more and more pronounced, until in 1959 the Arizona State Legislature formed the Maricopa County Flood Control District (MCFCD). The MCFCD became the lead player in developing a comprehensive flood plan for the entire county.

At the same time, the United States Army Corps of Engineers began to look into flooding in Maricopa County. Over the next several years, it presented several plans, which all revolved around constructing concrete canals and levees to channel and divert the floodwaters, as well as building bridges over the canal, similar to the storm drains of Los Angeles. But during MCFCD meetings between 1961 and 1963, a different course of action was developed. This plan became known as the multi-use, or Greenbelt, concept. The two concepts were at odds with one another until the canal plan was defeated in a bond referendum in 1965. In 1966 a study was commissioned that validated the Greenbelt concept as a way to prevent flood damage. After a major flood in 1972, work on the Greenbelt project began in earnest. It was completed in 1984, although minor projects continue. Today, the 12 mi (19 km) long Scottsdale Greenbelt connects four city parks—Vista del Camino Park, Eldorado Park, Indian School Park and Chaparral Park—through a 25 mi (40 km) bike path.

The 1960s and '70s continued to see the city's growth, the population reaching almost 68,000 by 1970. Most of the unused property within the city limits was to the north, so that was the direction in which the city expanded. The city, which in 1959 had spanned 5 square miles, expanded its borders to encompass 62 square miles. Large ranch tracts covered huge areas in the northern part of the city. One of the largest of these was the McCormick ranch, a 4,236-acre ranch serving much of the eastern boundary of Scottsdale owned by Fowler and Anne McCormick. Fowler's paternal grandfather was Cyrus McCormick, the inventor of the grain reaper, and his maternal grandfather was John D. Rockefeller. When Anne died in 1970, the property was sold to Kaiser-Aetna for $12.1 million. This started a series of large-scale, master-planned communities within Scottsdale's borders, including Scottsdale Ranch (1978), Gainey Ranch (1980), McDowell Mountain Ranch (1992), Desert Mountain (1986), and DC Ranch (1990s).

In 1975, the city annexed the "east Shea" section, bordering Fountain Hills, expanding its area from 62.2 to 88.6 square miles. This was followed by a four-year period from 1981 to 1984 during which the city annexed almost 80 additional square miles.

Faced with this rapid expansion and growth, many residents became concerned about losing their southwestern scenery. The McDowell Sonoran Conservancy was born in 1991. Teaming with developers, a plan was developed to set aside the McDowell Mountains and adjoining areas in a huge preserve. In 1995, Scottsdale's citizens voted to implement a sales tax to purchase acreage for this purpose. When completed, the 36,000 acres planned for the McDowell Sonoran Preserve will be nearly one-third of Scottsdale's land area, equal in size to Bryce Canyon National Park.

From its official incorporation in 1951 with a population of 2,000, Scottsdale has grown to a 2010 census count of 217,385. It is now the state's sixth-largest city. Scottsdale is commonly defined by its high quality of life, and in 1993 was one of several cities to receive a "Most Livable City" award from the United States Conference of Mayors.

As of the census of 2010, there were 217,385 people, there are 69,967 owner-occupied housing, 32,306 renter occupied, and 101,273 households in the city. The population density was 1,181.4 inhabitants per square mile (455.6/km²). There were 124,001 housing units at an average density of 673.9 per square mile (259.9/km²). The racial makeup of the city was 89.3% White, 1.7% Black or African American, 0.8% Native American, 3.3% Asian, 0.1% Pacific Islander, 2.5% from other races, and 2.3% from two or more races. 8.8% of the population were Hispanic or Latino of any race.

There were 101,290 households, out of which 20.0% had children under the age of 18 living with them. According to the 2010 census 51.7% of Scottsdale's population were females, while 48.3% were males. In the city the population was spread out, with 17.7% under the age of 18, 5.0% from 20 to 24, 32.6% from 25 to 49, 22.8% from 50 to 64, and 19.9% who were 65 years of age or older. The median age was 42 years.

According to a 2007 estimate, the median income for a household in the city was $80,533, and the median income for a family was $112,289. The per capita income for the city was $49,158. About 3.4% of families and 5.8% of the population were below the poverty line, including 5.4% of those under age 18 and 5.9% of those age 65 or over.

Scottsdale is home to a large number of churches, chapels, temples, synagogues, mosques and other places of religious worship. Though the majority of Scottsdale residents consider themselves of, or practicing of, the Christian faith(s) – including Protestant and Roman Catholic – the city's high population growth over the years has resulted in a more diverse population. Most notably, greater numbers of Eastern Orthodox and Jews have been added to the population. Though smaller in number, Hindu, Sikh and Buddhist communities also exist within the city of Scottsdale. There is also a small population of members of The Church of Jesus Christ of Latter-day Saints (Mormons), as is common throughout Phoenix, Arizona, and the Western United States.

The first church founded in Scottsdale was the First Baptist Church of Scottsdale, which was built by Scott and his family. The church has named a small non-profit coffee shop on the corner of their campus after Scott, called Winfield's.^{[citation needed]}

Congregation Beth Israel, the oldest Reform Judaism congregation in the Phoenix metropolitan area is in Scottsdale, and is the largest congregation in Arizona. In North Scottsdale, there is the Jewish Community Center of Phoenix and the New Shul. The community center was originally in central Phoenix, it had eventually outgrown the location and was looking to relocate and build a more expansive campus.

In 2009, a new Armenian Apostolic church was built in the city, representing the larger numbers of Armenians in the Phoenix Metropolitan Area.