Sophia Anna Bush was born on July 8, 1982, in Pasadena, California, to Maureen Searson, a photography studio manager, and Charles William Bush, an advertising and beauty photographer. She is of Italian (from her paternal grandfather), English, and Irish descent. Bush graduated from Westridge School for Girls in Pasadena in 2000, where she was a member of the volleyball team and debate team. She attended the University of Southern California, where she majored in journalism and minored in theatre. She was a member of the Kappa Kappa Gamma sorority.
Bush began her acting career in the early 2000s. Her first notable role was in the film Van Wilder (2002). She subsequently appeared in television shows such as Sabrina the Teenage Witch and Nip/Tuck before landing her breakthrough role as Brooke Davis in the WB/CW drama series One Tree Hill (2003-2012). She was a main cast member for all nine seasons of the show.
Following One Tree Hill, Bush continued to work in television. She starred as Detective Erin Lindsay in the NBC police procedural drama Chicago P.D. (2014-2017) and its associated franchise, appearing in Chicago Fire and Chicago Med. She also served as a director on several episodes of Chicago P.D.
In 2019, Bush starred in the CBS medical drama Good Sam, which premiered in 2022 and lasted for one season. She has also guest-starred in shows like Jane the Virgin and This Is Us.