[3] After he graduated from high school, his father began teaching history in northern Maine, while his mother continued to work in pottery.

[3][5] Williams graduated from Temple University with a double major in African American Studies and Film and Media Arts.

In 2012, he established a production company, farWord Inc.[5] In May 2012, a fan campaign was organized to try to influence film executives to cast him in the role of Finnick Odair in The Hunger Games: Catching Fire.

[11] Later that year he narrated the audio version of the book The Bane Chronicles: What Really Happened In Peru, by Cassandra Clare and Sarah Rees Brennan.

[13] On October 15, 2009, Williams began appearing as surgical resident Jackson Avery, in the ABC television series Grey's Anatomy.

In an interview with The Hollywood Reporter in May 2021, Williams said the decision to leave the show was "a collective thing" and part of a discussion the actor had with showrunner Krista Vernoff about Jackson's trajectory that ultimately helped solidify 11 seasons of storyline.

He subsequently appeared in Brooklyn's Finest (2009), starring Don Cheadle, Richard Gere, Ethan Hawke, Wesley Snipes, and Ellen Barkin.

Williams played Holden McCrea, the lead role in the MGM/United Artists horror film The Cabin in the Woods, produced by Joss Whedon and directed by Drew Goddard, released April 13, 2012.

[22] In May 2016, Williams was executive producer of the documentary film Stay Woke: The Black Lives Matter Movement, part of BET's 'The Truth Series'.

[23] In 2021, Williams produced an American short-film titled Two Distant Strangers, written by Travon Free and Martin Desmond Roe.

Williams has served as a guest director for student productions at the Urban Arts Partnership 24 Hour Plays Off-Broadway, at the request of Rosie Perez and Anna Strout.

Together with the rest of the cast, Williams was nominated for the Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Comedy Series in 2024.

He also did the voice acting and performance capture for Duke in the video game NBA 2K21, which released worldwide on September 4, 2020, for multiple consoles.