She was born in Atlanta, Georgia. While a student at Atlanta's Spelman College (the second oldest college for black women in the US) in 1974, she met actor Samuel L. Jackson, then at all-male Morehouse College, who would later become her husband. She and Jackson married in 1980. They have one child, freelance film and TV Producer Zoe Jackson, born in 1982. After her daughter's birth, Richardson stopped working regularly, because, she said: “We’d vowed to be an intact revolutionary black family. But it was very, very hard.”

Richardson has appeared in films include Fried Green Tomatoes (1991), Malcolm X (1992), Sleepless in Seattle (1993), When a Man Loves a Woman (1994), Losing Isaiah (1995), Lone Star (1996), U.S. Marshals (1998), and The Fighting Temptations (2003). Her television credits include Show Me a Hero, Luke Cage, and series regular role on the BET crime drama Rebel.

To date, Richardson's biggest role in a motion picture was in the 2003 musical The Fighting Temptations in which she appears as the main antagonist, the hypercritical Paulina Pritchett.

In 2014, Richardson was nominated for the Tony Award for Best Lead Actress in a Play for her 2013 performance in A Raisin in the Sun as Lena Younger, a role she took over at the last minute when Diahann Carroll dropped out due to health concerns. This was her second appearance on Broadway after her debut in the 2009 revival of Joe Turner's Come and Gone.