The City of Clayton acknowledges that it resides on the traditional homelands of the Osage Nation, Missouria, and Illini Confederacy. These Indigenous Peoples experienced significant loss of their land and culture due to the arrival and expansion of white settlers.

In 1876, when St. Louis City separated from St. Louis County, the county courts were left without a home. Ralph Clayton and Martin Hanley, two native Virginian farmers, donated land for the new county seat. The site was chosen over other remote villages and was named Clayton in honor of Ralph Clayton's contributions. Martin Hanley also donated a small plot east of Clayton's land, and today, their combined 104 acres form the City's Central Business District.

On December 4, 1877, Clayton was officially chosen as the new county seat. The new courthouse cornerstone was laid a few months later, and the building was completed at a cost of about $25,000. Over the next 25 years, Clayton grew from virgin forests and farmland to a small town, with businesses catering primarily to courthouse traffic.

In 1904, the Philippine Village at the World’s Fair covered 40 acres of what are now the Wydown-Skinker and DeMun neighborhoods. Designed to justify U.S. colonization of the Philippines, the exhibit displayed over 1,200 Filipinos in ethnological replicas of native villages. At least 17 individuals tragically died from pneumonia, malnutrition, suicide, and other consequences of this exploitation. As the city grew, the painful history of this exhibit, marked by abuse and suffering, was largely erased and forgotten.

The City of Clayton was formally incorporated in February 1913. Leaders in neighboring University City planned to annex Clayton, prompting Clayton residents to incorporate. On April 14, 1913, voters approved incorporation, and William Broadhead was chosen as the City's first mayor.

In the early 20th century, prominent St. Louisans began relocating to Clayton, leading to rapid growth. Between 1920 and 1925, Clayton's population grew from around 3,000 to more than 7,000, and the value of Clayton's real estate tripled.

During the Great Depression, Clayton's lack of manufacturing and heavy industry insulated it from the worst effects. Clayton built its first city hall in 1931 and completed several large civic initiatives under Mayor Charles Shaw, who served from 1933 to 1940. These included widening city streets, building a library, and creating Shaw Park.

 By the late 1940s, Clayton experienced a building and business boom that transformed it from a quaint suburb into the hub of the St. Louis metropolitan area. In 1952, the city re-zoned the area that became the Central Business District, allowing larger commercial and retail businesses to expand. This rezoning led to the displacement of a substantial and thriving Black community that had been part of Clayton since the 1880s. Despite facing nationwide and local discrimination and limited opportunities, Clayton's Black residents flourished as homeowners, educators, laborers, and business owners, enriching the cultural life of the community. As historic Clayton became the downtown business district, the history of our African American community was largely erased and forgotten.

In the mid-1950s, city officials realized the government needed restructuring and commissioned a task force to rewrite the city charter. Voters approved the new charter in February 1957, establishing a system where policy and planning were handled by the mayor and six aldermen, while administrative duties were given to a city manager.

The City abolished the height requirement on new buildings in 1957, leading to the construction of Clayton's first high rises in the early 1960s. Since then, Clayton has continued to grow and prosper, maintaining a safe, secure residential community while developing a bustling Central Business District. Over 81% of Clayton's real estate is either residential or city park, and Martin Hanley's 129-year-old farmhouse still stands on the edge of downtown Clayton, symbolizing the city's unique combination of urban flair and quiet community.

Today, Clayton is committed to honestly engaging with its history and ensuring it is never erased. In partnership with the Clayton Community Foundation, the City is working to restore and recognize erased histories through the installation of historical markers. The City strives to commemorate the experiences and honor the contributions of Indigenous Peoples, the Black community, Filipinos, and Indigenous Peoples from the Philippines, along with others whose histories are still being uncovered. These efforts are vital to understanding Clayton's complete history and promoting a more inclusive narrative for future generations.