In 1987, Prince-Bythewood graduated from Pacific Grove High School. She attended UCLA’s film school, where she also ran competitive track. At UCLA, she received the Gene Reynolds Scholarship for Directing and the Ray Stark Memorial Scholarship for Outstanding Undergraduates. She graduated in 1991.

In 1998 Prince-Bythewood married film director and writer Reggie Rock Bythewood, whom she met on the writing staff of A Different World. The couple have two sons, Cassius and Toussaint, and live in Southern California.

She directed the feature film The Secret Life of Bees, adapted from the best-selling book by Sue Monk Kidd. It was released by Fox Searchlight in October 2008, and debuted at the Toronto International Film Festival and Urbanworld Film Festival that same year.

In 2014, Prince-Bythewood directed Beyond the Lights, starring Gugu Mbatha-Raw. Prince-Bythewood began work on the film in 2007, before work on 2008’s The Secret Life of Bees was completed, but struggled to find financing when the original production company, Sony, backed out after she insisted on casting Mbatha-Raw. The film premiered at the 2014 Toronto International Film Festival.

In 2016 Prince-Bythewood announced her next project would be an adaptation of Roxane Gay’s novel An Untamed State. The project would be co-written by herself and Gay and would star Gugu Mbatha-Raw.

In 2017 Prince-Bythewood, along with her husband Reggie Rock Bythewood, created the show Shots Fired for Fox. Later that year, Prince-Bythewood was announced as the director for Silver & Black, a movie based on Marvel Comics characters Silver Sable and Black Cat.

In 2020, she and her husband signed a deal with Touchstone Television to produce their output using the banner “Undisputed Cinema.”