She is the longest-serving original cast member on the sketch comedy series Mad TV, having appeared on the show's first eight seasons from 1995 to 2003.

In 2022, Wilson started voicing Daisy Duck on Mickey Mouse Funhouse, making her the first African-American performer of the character.

Perhaps her best known character was the fast talking "Black American Princess" Bunifa Latifah Halifah Sharifa Jackson.

[13] Wilson has made numerous independent films, including Naked Angel, Jane White Is Sick and Twisted, Skin Deep, and Soulmates.

She appeared as herself on the February 15, 1999, episode of WCW Monday Nitro accompanying MADtv castmate Will Sasso in his professional wrestling match against Bret Hart.

Wilson is the announcer of the revival of the NBC game show Weakest Link hosted by Jane Lynch.

In July 2022, Nickelodeon announced that Wilson would voice the character Headless Headmistress Bloodgood in the 2022 animated reboot series Monster High.

Wilson performed off-Broadway with the improvisational comedy troupe Noo Yawk Tawk directed by Richmond Shepard at The Village Gate Theater (1988–1991).