A fifth-generation Mississippian, Samuel "Sambo" Mockbee was educated in Alabama and returned to his home state in 1977 to establish his first architectural practice with classmate and friend Thomas Goodman. He spent his life surrounded by the extreme poverty of the Deep South, and was committed to the belief that "everyone, rich or poor, deserves a shelter for the soul." His vision of the field fostered social and environmental change, embraced architectural education, and contributed to a strong sense of place by utilizing salvaged and vernacular materials.

Mockbee's best known designs were produced in partnership with Coleman Cocker, at their firm Mockbee Cocker, established in 1983. Their style has been described as contemporary Modernism grounded in Southern Culture. Many of their projects drew inspiration from elements of local architectural color such as overhanging galvanized roofs, rusting metal trailers, dogtrot forms, and porches. Their design process involved the creation of paintings, drawings, and writings that evolved in tandem with each new project. Their practice was loosely based on regional mythologies, tied to personal experience, and deeply involved with the rural towns and communities in which they built.

In 1991 Mockbee left his full-time architectural practice at Mockbee Cocker to accept a teaching position at Auburn University, under whose auspices he and his longtime friend and colleague, D.K. Ruth, conceived of and founded the Rural Studio in Hale County, Alabama. The Studio was a community-based program that taught architecture students the tenets of socially responsible design while providing cutting-edge architecture for some of the state's poorest communities. Largely on the basis of his work with the Studio, Mockbee was awarded a MacArthur Genius Grant in 2000. The following year, Mockbee lost his battle with leukemia, just three years after being diagnosed. The Rural Studio continues to construct homes and community facilities throughout Hale County.