While in New Zealand, Paquin attended Raphael House Rudolf Steiner School in Lower Hutt until she was 9 years old, then Hutt Intermediate School (1994–95). Having begun her secondary education in Wellington at Wellington Girls' College, she completed her high school diploma at Windward School in Los Angeles, after moving to the U.S. with her mother following her parents' divorce (1995). She graduated from Windward School in June 2000 and completed the school's Community Service requirement by working in a soup kitchen and at a Special Education Centre. She studied at Columbia University for one year but dropped out to continue her acting career.
Paquin played the mutant superhero Rogue in the Marvel Comics movie X-Men in 2000, its sequel X2 in 2003, and its third installment, X-Men: The Last Stand, in 2006. Between 2006 and 2007, she starred in, as well as executive-produced Blue State. The film is made by Paquin Films, a production company formed by her and her brother, Andrew Paquin. In November 2006, she completed the film Margaret, which was released in 2011. She played Elaine Goodale in HBO's made-for-TV film Bury My Heart at Wounded Knee, based on Dee Brown's best-seller. In 2007, she played the role of Laurie in the horror film Trick 'r Treat, which was released in 2009. Paquin was cast as waitress Sookie Stackhouse in the HBO series True Blood in 2008, her first role in a TV series. The show is based on The Southern Vampire Mysteries series of novels by Charlaine Harris, set in the fictional town of Bon Temps, Louisiana; which saw Paquin doing nude scenes for the first time. While working on True Blood, she started dating co-star Stephen Moyer and later married him in 2010.