Toussaint began her career in theatre, before supporting performances in films such as Breaking In (1989), Hudson Hawk (1991), and Dangerous Minds (1995).

She later appeared as a regular cast member in the NBC police procedural Crossing Jordan (2002–03) and the TNT crime drama Saving Grace (2007–10).

Toussaint received critical acclaim and an Independent Spirit Award nomination for her performance in the 2012 drama film Middle of Nowhere, written and directed by Ava DuVernay.

[8] Notable stage roles include Hippolyta in Liviu Ciulei's production of A Midsummer Night's Dream at the Guthrie Theater, Tamara in the world premiere of Toni Morrison's Dreaming Emmett at Capital Repertory Theatre, the American premiere of Two Fish in the Sky at the Phoenix Theatre, and an appearance at Tadashi Suzuki's Toga Festival in Japan.

In 1986, she portrayed the widow of a man shot and killed by Boston police in the television film A Case of Deadly Force, based on the book by Lawrence O'Donnell.

Toussaint made her film debut in the female lead role opposite Burt Reynolds in the crime comedy Breaking In (1989).

[14] Toussaint had her biggest and leading role alongside Annie Potts in the Lifetime first original television drama series, Any Day Now,[8] starring as Rene Jackson, a successful African-American lawyer.

The series received critical acclaim for both lead actresses' performances as well as the show's script writing[15][16][17] but never attained standout ratings.

[18] In 2001, Toussaint was a promising contender for a Primetime Emmy Award for Outstanding Lead Actress in a Drama Series category, though she did not receive a nomination.

She had a recurring role as Amelia 'Yoga' Bluman in the ABC comedy series Ugly Betty in 2006, and as Bird Merriweather in the NBC drama Friday Night Lights (2009–11).

[23] In 2013, she had a recurring role in season 3 of Dana Delany's series Body of Proof as villainous police chief Angela Martin.

[28][29] She played the role of Yvonne "Vee" Parker, the main antagonist of season two, described as a street-tough inmate who returns to jail after a long stint as a drug dealer.

[39][40] That same year, she was cast in the ABC fantasy-drama series Forever opposite Ioan Gruffudd and Alana de la Garza.

[46] In March 2016, Toussaint was cast in her role as defense attorney Shambala Green, a role she originated on Law & Order in 1990, on the NBC legal drama Chicago Justice, that aired a backdoor pilot in Chicago P.D..[47][48] On August 14, 2017, it was announced that Toussaint would join as a series regular in the third season of Into the Badlands.

[51] The following year, she played feminist, civil rights advocate and activist Florynce Kennedy in the biographical film The Glorias directed by Julie Taymor.