Blair, born in Southfield, Michigan, emerged from a background in legal and political involvement: both her parents were lawyers and her father active in the U.S. Democratic Party.

She initially pursued photography at Kalamazoo College before moving to New York to become involved in the arts, graduating from the University of Michigan.

Blair's early career was marked by numerous auditions to land her first roles in television and film, with her breakthrough in Cruel Intentions and subsequent mainstream success in projects like Legally Blonde and Hellboy.

[11] Intending to become a photographer, she attended New York University (NYU), and took acting classes at the Stella Adler Conservatory, the Column Theater, and Stonestreet Studios.

[24] The film made US$75.9 million internationally and brought Blair a nomination for the MTV Movie Award for Best Breakthrough Performance, and a win for "Best Kiss", shared with co-star Sarah Michelle Gellar.

[citation needed] In 2000, following her performance in the teen comedy Down to You, Blair won the Young Hollywood Award for "Exciting New Face".

[29] Blair co-starred in the 2001 hit comedy Legally Blonde, portraying a preppy, snobby law student; The Hollywood Reporter found her to be a "strong presence" in her role.

It premiered at the 2001 Cannes Film Festival; SPLICEDwire cited Blair and co-star Leo Fitzpatrick for "painfully authentic performances as an emotionally insecure coed and her cerebral palsy-stricken dorm neighbor and lover".

[32] In its review, View Auckland noted: "The acting, throughout, is excellent, with Selma Blair giving a mature performance that suggests better roles await her than those she's had so far.

[36][37] In 2004, Blair took on the role of Liz Sherman, a depressed pyrokinetic superhero,[38] in Guillermo del Toro's blockbuster fantasy film Hellboy, co-starring Ron Perlman.

Based on Mike Mignola's popular comic book series, the film was favorably received by critics; The New York Times remarked: "Blair's heavy-lidded eyes seem to be at half mast from some lovely lewd fantasy.

[40][41] Also in 2004, Blair played the role of an exhibitionist dancer in John Waters' satirical sex comedy A Dirty Shame, alongside Tracey Ullman.

Club described the production as a "proud retreat back into the sandbox of sexual juvenilia" and a "potty-mouthed manifesto from an elder statesman of shock", while pointing out that Blair and Ullman "throw themselves headfirst into the insanity, reveling in the forfeiture of dignity, self-respect, and self-consciousness their roles demand".

In 2010, Blair she lent her voice to narrate the audiobook of The Diary of a Young Girl: The Definitive Edition, originally written by Holocaust victim Anne Frank.

In 2012, Blair returned to television as the female lead with the premiere of FX's Anger Management, co-starring Charlie Sheen.

[57][58] Blair left the show in June 2013, during the shooting of the second season, due to disagreements with Sheen, who fired her via text message.

The film focuses on Alon Shamriz, Yotam Haim, and Samer Talalka, three Israeli men taken hostage by Hamas during the October 7 attack on Israel.

[76][77] She lent her image to the Marc Jacobs-Brian Bowen Smith clothing line,[78][79] and has worked with several other fashion designers, including Karen Zambos, Martin Margiela, Isaac Mizrahi, Reinaldo Herrera, and Stella McCartney.

[80][81][82][83][84] She was featured in the 2002 Pirelli Calendar,[85] and, in 2005, appeared in The New York Times Magazine award-winning photography gallery, "The Selma Blair Witch Project: Fall's Dark Silhouettes Have a Way of Creeping Up on You" by the art photographer Roger Ballen, at the Palau Robert in Barcelona in 2012.

[86][87] Blair also appeared with Rainn Wilson singing "Baby, It's Cold Outside" for the 2008 Gap winter ad campaign, and was included in Glamour's list of the 50 Most Glamorous Women of 2008.

[93] In 1999, she appeared in Seventeen, and in subsequent years, in Vanity Fair, Marie Claire, Vogue, Glamour, Rolling Stone, The Lab Magazine, Interview, Dazed & Confused, Hunger, and Elle.

[96] She presented parts of the collection of Christian Siriano at a celebration of his 10th stage anniversary at Masonic Hall during New York Fashion Week 2018.

[97] On January 24, 2004, Blair married writer and producer Ahmet Zappa at Carrie Fisher's mansion in Beverly Hills, California.

[110] In a 2023 interview with British Vogue, Blair said that her symptoms had begun to manifest themselves when she was a child, and that her un-diagnosed MS had caused brain damage.

In June 2022, Blair became chief creative officer of Guide Beauty, a company which creates cosmetic products for those with mobility challenges.

[133][134][135] In September 2024, Blair again expressed support for Israel and the hostages taken by Hamas, and said that Gaza was being run by "Jihadists, the radicals, the extreme" and "terrorists".