King began her acting career in 1985 playing the role of Brenda Jenkins on the television series 227, a role she played until the show ended in 1990. She went on to appear in the John Singleton films Boyz n the Hood, Poetic Justice and Higher Learning. In 1995, she was featured in the hit comedy film Friday. In 1996, she starred in the Martin Lawrence dark comedy-romance A Thin Line Between Love and Hate as Mia. Later in 1996 she gained fame starring in the blockbuster romantic comedy film Jerry Maguire as Marcee Tidwell, the wife of Cuba Gooding, Jr.'s character. She played Will Smith's character's wife in Enemy of the State, and was also featured in How Stella Got Her Groove Back, Mighty Joe Young, Down to Earth, Daddy Day Care, Legally Blonde 2: Red, White & Blonde, A Cinderella Story, Ray and Miss Congeniality 2: Armed and Fabulous.
Beginning in the mid-2000s, she had ongoing roles on several TV series, including acclaimed work as the voice of Huey and Riley Freeman for the animated series The Boondocks and Detective Lydia Adams on the TNT police drama Southland. She also appeared in roles on 24, The Big Bang Theory, and Shameless. In 2007 she played Lisa Moore in This Christmas. She was a cast member on ABC's John Ridley-penned ensemble drama American Crime, and played a devout member of the Nation of Islam and sister to a drug addict accused of murder. In September 2015 and September 2016, King won the Primetime Emmy Award for Outstanding Supporting Actress in a Limited Series or a Movie for American Crime. In 2018, she played the role of the mother of a murdered black teenager in Netflix original series Seven Seconds, winning her third Primetime Emmy Award. Her performance in the 2018 film If Beale Street Could Talk, directed by Barry Jenkins, garnered critical acclaim and earned her the Academy Award for Best Supporting Actress.