He reprised his role in the acclaimed 2003 HBO miniseries adaptation, earning the Primetime Emmy Award for Outstanding Supporting Actor in a Limited Series or Movie.

He also appeared as Isaac Dixon in the video game The Last of Us Part II (2020) and the Watcher in the Marvel Studios animated series What If...?

After attending the MFA acting program at the New York University Tisch School of the Arts for two months in 1988, he left to appear in Les Blancs at Arena Stage before transferring with it to the Huntington Theatre Company and deciding to be an actor full-time.

[7] His portrayal of a gay nurse forced to take care of Roy Cohn as he dies of AIDS won him the Tony Award for Best Featured Actor in a Play.

He guest-starred in George Lucas's The Young Indiana Jones Chronicles as a fictionalized Sidney Bechet and Homicide: Life on the Street in the early to late 1990s.

[9] Throughout the 1990s and early 2000s, he appeared in roles in such films as Woody Allen's satirical comedy Celebrity (1998), and Ang Lee's western Ride with the Devil (1999).

He also starred in Clark Johnson's HBO television film Boycott (2001) as Martin Luther King Jr., for which he received an AFI Award.

[12] In 2003, he reprised his role as Norman "Belize" Arriaga in HBO's award-winning adaptation of Angels in America, garnering him an Primetime Emmy Award for Outstanding Supporting Actor in a Limited or Anthology Series or Movie and a Golden Globe Award for Best Supporting Actor – Series, Miniseries or Television Film.

[14] In 2005, he played Washington attorney Bennett Holiday in Syriana and Bill Murray's eccentric Ethiopian neighbor Winston in Broken Flowers, the latter of which earned Wright a Independent Spirit Award for Best Supporting Male nomination.

[17] In 2010, Wright played Jacques Cornet in the world premiere run of A Free Man of Color at the Vivian Beaumont Theater of the Lincoln Center for Performing Arts in New York City.

[24] In 2018, Wright produced the HBO documentary We Are Not Done Yet, which gives voice to war veterans who, through a USO-sponsored arts workshop at Walter Reed National Military Hospital, discover the power and healing of shared experience to unite and find resilience in the face of post-traumatic stress.

[25] That same year, Wright starred in HBO's O.G., a film about a man confronting his past crime and preparing to leave prison after decades behind bars.

[29] Nick Paumgarten of The New Yorker said, "The performances are exceptionally strong, both by the free-to-leave professional actors (especially Jeffrey Wright, who plays Louis, the 'O.G.'

"[30] Ben Kenigsberg of The New York Times said, "Jeffrey Wright gives a rich, imposing performance as the former 'mayor' of Pendleton Correctional Facility.

"[31] In 2019, he acted in the Steven Soderbergh directed Netflix comedy-drama The Laundromat starring Meryl Streep, Antonio Banderas, and Gary Oldman.

[32] He also acted in John Crowley's drama The Goldfinch starring Nicole Kidman, Sarah Paulson, and Finn Wolfhard.