As a teenager, Smith was among the first students to integrate the public schools in Macon County, Alabama, over the protests of state officials in the administration of Governor George C. Wallace.

Ultimately, Smith was one of 12 students to file a lawsuit against the Macon County Board of Education to preserve their legal right to attend the previously all-white Tuskegee High School.

[1] In 1998, Smith was appointed to head the FAA's newly created Office of Commercial Space Transportation, a position she held until 2008.

[6][7] In April 2012, Smith was invited to be a member of the advisory board of the National Air and Space Museum by President Obama.

"[11] The Patti Grace Smith Fellowship was set up in 2020 to provide "Jobs, Mentorship, and Community for Black Undergrads Seeking Aerospace Careers".