The territory of present-day Oklahoma was long settled by ancient cultures of prehistoric American Indians, including the Clovis, 11500 BCE; Folsom, 10600 BCE; and Plainview, 10000 BCE cultures.

The valleys of the Arkansas River and Red River were the center of Caddoan Mississippian culture, which began to develop about 800 CE. The people developed more dense settlement and a complex architecture of earthwork platform mounds. Archeological evidence has shown that these people were the direct ancestors of the historic Caddoan-language peoples who inhabited the larger region, including the Caddo and the Wichita peoples.

In the 16th century, Spanish explorer Francisco Vásquez de Coronado visited in 1541, beginning European contact. Around the 1700s, two tribes from the north, the Comanche and Kiowa, migrated to the Oklahoma and Texas regions.

For most of the 18th century, the French exerted nominal control over the Oklahoma region as part of their La Louisiane, or New France. The largest French settlements were along the Gulf Coast, in New Orleans, Louisiana, and Mobile, Alabama. The limited interaction between the Native American and European peoples was based on fur trading.

In 1803, the French sold this territory as Louisiana Purchase to the US, under President Thomas Jefferson. European Americans continued to migrate into the Southeast and across the Mississippi River into Indian territories, especially seeking territory to expand cotton cultivation, which was a lucrative commodity crop. They pressured the government to give them access to Indian lands. In 1830, under President Andrew Jackson, Congress passed the Indian Removal Act, which removed American Indian tribes from the Southeast and relocated them to Indian Territory west of the Mississippi River.

The southern part of this territory was originally assigned to the Choctaw and Chickasaw. Following the Civil War, during which most of the Southeast tribes had allied with the Confederacy, in 1867, the United States required new treaties of peace. In 1867, under the Medicine Lodge Treaty, it allotted the southwest portion of former Choctaw and Chickasaw lands to the Comanche, Kiowa, and Apache tribes. It had forced them to move out of East Texas and nearby areas of Arkansas.

Fort Sill was established in 1869 after the American Civil War and commanded by Major General Philip Sheridan. He was leading a campaign in Indian Territory to stop raids into Texas by American Indian tribes. In 1874, the Red River War broke out in the region when the Comanche, Kiowa, and Southern Cheyenne left their Indian Territory reservation. Attrition and skirmishes by the US Army finally forced the return of the tribes to Indian Territory in June 1875.

In 1891, the United States Congress appointed a commission to meet with the tribal leaders and come to an agreement allowing White settlement. Years of controversy and legal maneuvering ensued before President William McKinley issued a proclamation on 4 July 1901, that gave the federal government control over 2,000,000 acres (8,100 km²) of "surplus" Indian lands that remained after allotments of communal tribal lands to individual households under the Dawes Act. Under other legislation, the United States through the Dawes Commission allotted communal lands as plots to individual households of tribal members, selling off what remained as "surplus". These actions extinguished the tribal claims to communal lands, a condition needed for the admission of Oklahoma as a state in 1907.

After these changes, the legislature of the new state began to organize counties. Three 320-acre sites in Kiowa, Caddo and Comanche counties were selected for county seats. Lawton was designated as the Comanche County seat. The town was named for Major General Henry W. Lawton, a quartermaster at Fort Sill, who had taken part in the pursuit and capture of Comanche chief Geronimo.

The city was opened to settlement through an auction of town lots beginning on 6 August 1901, which was completed 60 days later. By 25 September 1901, the Rock Island Railroad expanded to Lawton and was soon joined by the Frisco Line. The first city elections were held 24 October 1901.

The United States' entry into World War I accelerated development at Fort Sill and Lawton. The availability of 5 million US gallons (19,000 m³) of water from Lake Lawtonka, just north of Fort Sill, was a catalyst for the War Department to establish a major cantonment named Camp Doniphan. It was active until 1922.

Similarly, the US response in World War II stimulated activity and expansion at Fort Sill and Lawton. The city's population increased from 18,055 to 34,757 from 1940 to 1950. By the 1960s, it had reached 61,697.

In the postwar period, Lawton underwent tremendous growth during the late 1940s and 1950s, leading city officials to seek additional water sources to supplement existing water from Lake Lawtonka. In the late 1950s, the city purchased large parcels of land along East Cache Creek in northern Comanche County for the construction of a dam and man-made lake, built in 1959 on the creek just north of U.S. 277 west of Elgin. Lake Ellsworth, named for a former Lawton mayor, soft-drink bottler C.R. Ellsworth, was dedicated in the early 1960s. It offered additional water resources, but also recreational opportunities and flood control along Cache Creek.

In 1966, the Lawton City Council annexed several square miles of land on the city's east, northeast, west, and northwest borders, expanding east beyond the East Cache Creek area and west to 82nd Street. On 1 March 1964, the north section of the H. E. Bailey Turnpike was completed, connecting Lawton directly to Oklahoma City, the capital. The south section of the turnpike leading to the Texas border was completed on April 23, 1964.

Urban-renewal efforts in the 1970s transformed downtown Lawton. A number of buildings dating to the city's founding were demolished to build an enclosed shopping mall, which was believed to provide a suburban attraction for shoppers.

On 23 June 1998, the city expanded when Lawton annexed neighboring Fort Sill. The Base Realignment and Closure of 2005 resulted in reassignment of people from other bases and consolidation of some military activities at Fort Sill, increasing the number of people assigned there and its scope of activities. Lawton expects a continuing benefit if population and economic growth over the course of the next 20 years.

As of the census of 2010, 96,867 people, 34,901 households, and 22,508 families resided in the city. The population density was 1,195.4 people per square mile (461.5/km²). The 39,409 housing units averaged 486.3 per square mile (187.8/km²). The racial makeup of the city was 60.3% White, 21.4% African American, 4.7% Native American, 2.6% Asian, 0.3% Pacific Islander, 3.4% from other races, and 4.9% from two or more races. Hispanics or Latinos of any race were 12.6% (7.8% Mexican, 2.8% Puerto Rican, 0.3% Panamanian).

Of the 34,901 households, 36.6% had children under the age of 18 living with them, 43.8% were married couples living together, 15.8% had a female householder with no husband present, and 35.5% were not families. Of all households, 29.4% were made up of individuals, and 2.3% had someone living alone who was 65 years of age or older. The average household size was 2.48 and the average family size was 3.08.

In the city, the population was distributed as 24.9% under the age of 18, 15.3% from 18 to 24, 30.2% from 25 to 44, 20.3% from 45 to 64, and 9.4% who were 65 years of age or older. The median age was 29 years. For every 100 females, there were 108.1 males. For every 100 females age 18 and over, there were 110.0 males.

The median income for a household in the city was $41,566, and for a family was $50,507. Males had a median income of $36,440 versus $31,825 for females. The per capita income for the city was $20,655. About 16.6% of families and 19.0% of the population were below the poverty line, including 33.5% of those under age 18 and 4.9% of those age 65 or over.