Bush has also appeared in films, including John Tucker Must Die (2006), The Hitcher (2007), The Narrows (2008), Chalet Girl (2011), Marshall (2017), Acts of Violence (2018), and Incredibles 2 (2018).

Bush currently co-hosts the Drama Queens podcast along with her former One Tree Hill co-stars, Bethany Joy Lenz and Robert Buckley.

Following this, she made appearances in several television shows, including Nip/Tuck, Sabrina the Teenage Witch, and the HBO film Point of Origin.

In 2002, Bush was cast as Kate Brewster in Terminator 3: Rise of the Machines, though she was replaced by Claire Danes after a week of filming.

[7] Jonathan Mostow, the director of the film, stated that he had replaced her as he felt she was too young for the role, but praised her talent as an actress.

[9] Bush and her One Tree Hill co-stars were endorsers for MasterCard, Kmart, Chevy Cobalt and Cingular Wireless.

[13] In July 2006, Bush co-starred in the 20th Century Fox comedy film John Tucker Must Die, directed by Betty Thomas, opposite Brittany Snow and Jesse Metcalfe.

That same year, she also starred in Buena Vista Pictures' supernatural thriller Stay Alive alongside Jon Foster, Frankie Muniz, and Adam Goldberg.

[14] She played Grace Andrews in the 2007 remake of the classic horror film The Hitcher, starring opposite Sean Bean.

In 2008, Bush co-starred alongside Kevin Zegers and Vincent D'Onofrio in François Velle's independent film The Narrows, playing Kathy Popovich.

[18] That same year, she was cast in a main role in the television pilot Hatfields & McCoys, but the project failed to be picked up to series.

[26] Since 2021, Bush has been a co-host on the Drama Queens podcast along with her former One Tree Hill co-stars, Hilarie Burton Morgan and Bethany Joy Lenz.

[31] Bush became engaged to her One Tree Hill co-star Chad Michael Murray in May 2004,[32] and they married on April 16, 2005, in Santa Monica, California.

[50][51] In April 2024, Bush confirmed her relationship with former professional soccer player Ashlyn Harris and came out as queer in an article in Glamour that she wrote.

[54] In April 2009, along with stars Sarah Chalke, Jason Lewis, Alicia Silverstone, Jane Lynch, and Lance Bass, Bush appeared in the Funny or Die video "A Gaythering Storm", which parodied a National Organization for Marriage video objecting to same-sex marriage.

[57][58] Bush set up a fundraiser intended to help people living in the area of the Gulf of Mexico affected by the environmental disaster of the Deepwater Horizon oil spill on April 20, 2010.

The actress, to support the fundraiser, announced that she would be running a half marathon that following November, despite having asthma and a year-old knee injury.

She was chosen as the spokesperson to endorse the launch of eMission, a Facebook game with the social mission to engage America's youth in fighting climate change created through the joint efforts of Do Something and U.S. Environmental Protection Agency's (EPA) Energy Star program.

[64] In 2011, Bush also became involved in the Pencils of Promise organization, which builds schools and increases educational opportunities in the developing world.

Two of her contributions include creating a clothing line benefiting Planned Parenthood and giving a speech at the Women's March on January 20, 2018.

[72] Sophia is also constantly using her social media platforms, such as Twitter, encouraging people to participate in the ongoing activism opportunities around the world.

In the 2018 fight over the nomination of Brett Kavanaugh to the Supreme Court, Bush was supportive of Christine Blasey Ford, and praised her "strength" throughout the controversy.

In July 2022, Bush and Grant Hughes wrote an essay for Glamour affirming their support of abortion rights in the wake of the Supreme Court issuing the decision of Dobbs v. Jackson Women's Health Organization that subsequently overturned Roe v. Wade.

In November 2024, Bush signed an exclusive partnership agreement with Washington Speakers Bureau (WSB), where she advocates for economic growth, women's empowerment, and community engagement.

[76] In 2018, Bush helped found a nonpartisan movement with Mandana Dayani that aims to create a cultural shift around voting and civic engagement by unifying around a central truth: democracy works best when we all participate.

Their campaign to boost voter registration included participants Debra Messing, Eric McCormack, Sean Hayes, Gwyneth Paltrow, Robert Downey Jr., Jennifer Aniston, Lisa Kudrow, Courteney Cox, Bush, Hilarie Burton, and Bethany Joy Lenz.

[79] She also appeared on the cover of the November 2006 edition of Maxim with her One Tree Hill co-stars Hilarie Burton and Danneel Harris.

[80] Bush has been featured in several fashion blogs and magazines, including CosmoGirl, Health, Lucky, Zooey, Saturday Night, Teen People and Bello.