Bassett soon looked for acting work in the New York theater. One of her first New York performances came in 1985 when she appeared in J. E. Franklin's Black Girl at Second Stage Theatre. She appeared in two August Wilson plays at the Yale Repertory Theatre under the direction of her long-time instructor Lloyd Richards. The Wilson plays featuring Bassett were Ma Rainey's Black Bottom (1984) and Joe Turner's Come and Gone (1986). In 2006, she had the opportunity to work on the Wilson canon again, starring in Fences alongside longtime collaborator Laurence Fishburne at the Pasadena Playhouse in California.
In 1992, Bassett played Katherine Jackson in the mini series The Jacksons: An American Dream. Later that year, Bassett was cast as Tina Turner in the feature film What's Love Got to Do with It (1993). Bassett won a Golden Globe and earned an Academy Award nomination for her portrayal of Turner. She was the first African-American to win the Golden Globe Award for Best Actress – Motion Picture Musical or Comedy.
Bassett starred in three movies in 1995, which were released with varied reactions from critics: Vampire in Brooklyn, Strange Days, and Waiting to Exhale (where she worked with author Terry McMillan). In Strange Days, Bassett plays Lornette "Mace" Mason, a chauffeur and bodyguard. In Vampire in Brooklyn, she plays Rita Veder, a tortured cop with a dark secret. Bassett's character in Waiting to Exhale, Bernadine Harris, was betrayed by her husband and in revenge she set fire to his entire wardrobe and vehicle, then sold what was left for one dollar.
In 2003, she read from the WPA slave narratives in the HBO film Unchained Memories. In the 1930s, about 100,000 former slaves were still living during the Great Depression, of which 2,300 were interviewed part of the Federal Writers' Project. The transcripts of the Slave Narratives collection of the Library of Congress is a record of slavery, bondage and misery.
Bassett joined the regular cast of the medical drama series ER for the show's final season (2008–2009). She portrayed Dr. Catherine Banfield, an exacting Chief of the ER who was also working to recover from the death of a son and to bring another child into her family. Bassett's husband Courtney Vance played her television husband on ER as Russell Banfield.
In 2010, Basset lent her voice to portray First Lady Michelle Obama on an episode of The Simpsons entitled "Stealing First Base". Bassett was also cast in the superhero film Green Lantern, to be released in 2011, as notable DC Comics character Amanda Waller.
In 2010, Deadline.com reported that Bassett would have a role in ABC's show, One Police Plaza.
Bassett married actor Courtney B. Vance in 1997. In the summer of 2005, they starred together in a production of the play His Girl Friday at the Guthrie Theater in Minneapolis, Minnesota. Trying for seven years since 2000, Bassett suffered two miscarriages. The couple's children -- son Slater Josiah and daughter Bronwyn Golden-- were born on January 27, 2006 in California via surrogate.
Bassett is represented by the Executive Speakers Bureau of Memphis, Tennessee and receives over $50,000 per appearance.
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