2012–present
In 2012, Toussaint received critical acclaim and was nominated for an Independent Spirit Award for Best Supporting Female for her performance as a hardworking mother who struggles to support her daughter's (Emayatzy Corinealdi) decision to put her life on hold to support her incarcerated husband (Omari Hardwick), in Middle of Nowhere, a drama film written and directed by Ava DuVernay. Toussaint was a promising contender for an Academy Award for Best Supporting Actress category in 2013, but she did not receive a nomination.
In 2012, she guest-starred in Shonda Rhimes' dramas Grey's Anatomy (as a doctor) and Scandal (as a bereaved and betrayed pastor's wife). In 2013, she had a recurring role in season 3 of Dana Delany's series Body of Proof as villainous police chief Angela Martin. Later in 2013, she joined the cast of ABC Family drama series, The Fosters, as Sherri Saums character's mother. This marked the first time she reunited on-screen with Annie Potts since the finale of Any Day Now in 2002.
Toussaint starred in the second season of Netflix's original comedy-drama series, Orange Is the New Black in 2014. 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. Her performance earned critical acclaim. In the series Toussaint, in her 50s, appeared nude on-screen for the first time in her career. For her performance, she won the Critics' Choice Television Award for Best Supporting Actress in a Drama Series and the Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Comedy Series. In February 2016, Vee was ranked 28th on Rolling Stone's list of "40 Greatest TV Villains of All Time".
In 2014, Toussaint co-starred in Ava DuVernay's historical drama film Selma, playing Amelia Boynton Robinson, a leading civil rights activist who had a key role in efforts that led to passage of the Voting Rights Act, and who was the first African-American woman in Alabama to run for Congress. That same year, she was cast in the ABC fantasy-drama series Forever opposite Ioan Gruffudd and Alana de la Garza. The series was canceled after a single season. Toussaint co-starred in the comedy film Xmas, directed and written by Jonathan Levine, which was released on November 25, 2015. Also in 2015, she co-starred in Runaway Island and Sophie and the Rising Sun. Later that year, Toussaint was cast in Coco, a drama produced by Lionsgate, alongside rapper Azealia Banks. In June 2015, she joined the cast of the Fox comedy-drama Rosewood in the series regular role of the titular character's mother.
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.. On August 14, 2017, it was announced that Toussaint would join as a series regular in the third season of Into the Badlands. She played the role of Cressida, a self-styled Prophetess in season 3.
In 2019, Toussaint starred in the NBC limited drama series The Village. The series was canceled after one season. She later starred in the superhero film Fast Color opposite Gugu Mbatha-Raw and played the role of Louise "Lou Lou" Baptiste in the horror film Scary Stories to Tell in the Dark produced by Guillermo del Toro. The following year, she played feminist, civil rights advocate and activist Florynce Kennedy in the biographical film The Glorias directed by Julie Taymor. The film premiered at the Sundance Film Festival on January 26, 2020. Later, she was cast opposite Idris Elba in the drama film Concrete Cowboy. Also in 2020, Toussaint was cast as Viola "Aunt Vi" Lascombe in the CBS reboot of The Equalizer starring Queen Latifah.