After studying at the College of William & Mary he started a career in journalism and wrote for numerous publications before becoming an editor at Gawker until 2014.

He made his feature directorial debut with the satire American Fiction (2023), for which he received a nomination for Best Picture and won Best Adapted Screenplay at the 96th Academy Awards.

His maternal grandfather was shocked by his daughter's choice to marry a black man, and he shut her and his grandson out of his life.

[3] Jefferson wrote a personal essay on the experience, noting that he was treated for atrial fibrillation and that, after surgery, he quit smoking and began to take better care of his health.

He also wrote for publications including USA Today, Huffington Post, The Root, and The New York Times Magazine.

Jefferson then became a story editor and consulting producer for Aziz Ansari's Netflix comedy series Master of None (2017) and the Mike Schur-created NBC sitcom The Good Place (2017–2019), for which he received Writers Guild of America Award nominations.