Theron grew up on a farm near Benoni, S.Af. At age 13, wanting to continue her ballet studies, she began attending a boarding school that specialized in the arts. During a visit home when she was 15, her mother shot and killed her father in self-defense after being attacked by him while he was drunk. At age 16 Theron moved to Milan to work as a model. Two years later she settled in New York City, where she continued to model and began studying at the Joffrey Ballet School. A knee injury ended her chances of a career in dance, however, and she attempted, unsuccessfully, to pursue acting jobs.

Theron eventually moved to Hollywood, and while making a loud scene after a bank refused to cash a check, she was discovered by an agent. She subsequently began landing some small parts, one of which—in 2 Days in the Valley (1996)—gained her favourable notice and paved the way for her first lead, in The Devil's Advocate (1997). That film showcased her acting ability and versatility and led to further substantial roles, notably in Mighty Joe Young (1998), Celebrity (1998), The Cider House Rules (1999), and The Italian Job (2003). Her acting talent was further expressed in her award-winning performance as serial killer Aileen Wuornos (Wuornos, Aileen) in Monster. Theron's immersion in the role—she became almost unrecognizable, thanks partly to a nearly 30-lb (14-kg) weight gain—helped her become the first South African to win an Oscar for best actress.

Theron appeared in two movies in 2004, The Life and Death of Peter Sellers and Head in the Clouds. Her performance as a miner battling sexual harassment in North Country (2005) earned Theron an Academy Award nomination for best actress. Her later films include In the Valley of Elah (2007) and Hancock (2008).