Lathan was born in New York City. Her first name means "artistry" in Swahili and "shining light" in Arabic. Her mother, Eleanor McCoy, was an actress and dancer who performed on Broadway with Eartha Kitt. Her father, Stan Lathan, worked behind the scenes in television for PBS, as well as a producer on shows such as Sanford & Son and Russell Simmons' Def Comedy Jam. Her brother is Tendaji Lathan, a well known DJ. She attended Manhattan Center for Science and Mathematics.
She graduated from the University of California, Berkeley with a bachelor's degree in English. Lathan then attended Yale University, and earned a master's degree in drama.
Following her training at Yale, where she studied with Earle R. Gister and performed in a number of Shakespeare's plays, Lathan earned acclaim both off-Broadway and on the Los Angeles stage. Encouraged by her father to make Los Angeles her professional base, Lathan found early television roles on episodes of such shows as In the House, Family Matters, NYPD Blue, and Moesha. During that same period, she won raves and a Best Actress nod from the Los Angeles NAACP Theatrical Award Committee for her performance in To Take Arms.
In 1998, Lathan earned a degree of recognition with her role as the mother of Wesley Snipes' title character in Blade. She followed this the subsequent year with a role in Life with Martin Lawrence and Eddie Murphy and back-to-back turns in The Best Man and The Wood. The Best Man was a comedic ensemble film, starring Taye Diggs, Nia Long, Harold Perrineau Jr., and Morris Chestnut. The Best Man went on to become one of the top ten highest grossing African American films in history and Lathan received a NAACP Image Award nomination for her performance. The Wood, another ensemble film starring Diggs and Omar Epps, cast her as the love interest of Epps. Lathan and Epps were reunited onscreen in Gina Prince-Bythewood's Love & Basketball, this time playing a couple as passionate about basketball as they are about each other. Her performance in Love & Basketball earned her the 2001 NAACP Image Award for Outstanding Actress in a Motion Picture, as well as an Independent Spirit Award nomination for Best Actress and a BET Award. In 2000, Lathan appeared in the Off-Broadway production of The Vagina Monologues along with Teri Garr and Julianna Margulies.
In 2001, Lathan earned additional acclaim for her work in the multicultural comedy film Catfish in Black Bean Sauce. Next was her second collaboration with Prince-Bythewood: Disappearing Acts; it is based on a novel by Terry McMillan. In the HBO film, Lathan is cast as an aspiring singer/songwriter in love with a carpenter, played by her Blade co-star Wesley Snipes. For her work in the film, Lathan earned an Essence Award for Best Actress. That year, she was named by Ebony magazine as one of its 55 Most Beautiful People and was honoured by Essence magazine and Black Entertainment Television. In 2002, Lathan starred in the romantic comedy film, Brown Sugar, alongside Diggs, Queen Latifah, and Mos Def. Lathan's performance earned an NAACP Image Award Nomination for Outstanding Actress in a Motion Picture. The film also received an NAACP Image Award nomination for Outstanding Motion Picture. In 2004, Lathan starred on Broadway in A Raisin in the Sun with Sean Combs, Audra McDonald, and Phylicia Rashad. Lathan received a Tony Award nomination for Best Performance by a Featured Actress for her portrayal of Beneatha Younger. Several years later, Lathan reprised the role in a critically acclaimed ABC Network production of A Raisin in the Sun.
In 2003, she co-starred with Denzel Washington in Out of Time. The following year, she was cast in the lead role in Alien vs. Predator. The film was a major success grossing over $171 million worldwide.
Lathan has acted in several roles in which her characters are involved in interracial relationships. In 2006, she co-starred with Simon Baker in Something New, a romantic comedy; as Michelle Landau, the much younger wife of a Texas businessman (Larry Hagman) during the fourth season of the television series, Nip/Tuck; and in 2008 as Andrea in Tyler Perry's The Family That Preys. The film also features Alfre Woodard and Kathy Bates; it was released in the U.S. on September 12, 2008. In an interview with NPR, Lathan said the script took a fresh approach to telling an interracial love story, by describing the internal conflict some African-American women confront when it comes to dating interracially. "I feel like with black women, in a way, I feel like it has been harder for us to go there just in terms of culturally. I know that there's this statistic that says that like 13 percent of black men are in interracial relationships. And don't quote me on this, but it's like four percent or three percent of black women are in interracial relationships; and I think that says a lot about, you know, either black women's loyalty her black man or her either guilt about stepping outside of the race."
In 2009, Lathan co-starred with Matthew Broderick in the drama Wonderful World. From 2009 to 2013, she voiced the character Donna Tubbs on The Cleveland Show.
In 2011, Lathan co-starred in the Steven Soderbergh thriller Contagion alongside Matt Damon, Jude Law, Marion Cotillard, Kate Winslet, Gwyneth Paltrow, Bryan Cranston, and Laurence Fishburne. In 2011, Lathan starred alongside Anthony Mackie and Forest Whitaker in Repentance, a psychological thriller directed by Phillipe Caland. Lathan played series regular Mona Fredricks in the second season of Starz' original series Boss, starring Kelsey Grammer.