Prince-Bythewood was born in Los Angeles, California, and adopted by Bob Prince, a computer programmer, and Maria Prince, a nurse, when she was 3 weeks old. Her adoptive father is white and her adoptive mother is of Salvadoran and German descent. She grew up in the middle-class neighborhood of Pacific Grove, California. She has four siblings through her adoptive family.
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.
She sought out her birth mother around 2014, but it was "not a positive experience". Her birth mother, who is white, was a teenager when she gave her up for adoption, because her family knew her child would be multiracial and they wanted her to have an abortion.

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