Director Jane Campion was looking for a little girl to play a main role in The Piano, set to film in New Zealand, and a newspaper advertisement was run announcing an open audition. Paquin’s sister read the ad and went to try out with a friend; this inspired Paquin to audition. When Campion met Paquin—whose only acting experience had been as a skunk in a school play—she was very impressed with the nine-year-old’s performance of the monologue about Flora’s father, and she was chosen from among the 5000 candidates. When The Piano was released in 1993 it was lauded by critics, won prizes at a number of film festivals, and eventually became a popular film among a wide audience. Paquin’s debut performance in the film earned her the 1993 Academy Award for Best Supporting Actress at the age of 11, making her the second-youngest Oscar winner in history, behind Tatum O’Neal.

The Piano was made as a small independent film and wasn’t expected to be widely known, and Paquin and her family did not plan to continue to pursue acting. However, she was invited to the William Morris Agency, and she kept receiving offers for new roles. She systematically rejected them, but she did appear in three commercials for the phone company MCI in 1994. She later made a series of television commercials for Manitoba Telecom Systems in her birth city of Winnipeg. She also appeared as a voice in an audiobook entitled The Magnificent Nose in 1994.

In 1996, she appeared in two films. The first role was as young Jane in Jane Eyre. The other was a lead part in Fly Away Home playing a young girl who, after her mother dies, moves in with her father and finds solace in taking care of orphaned goslings. As a teenager, she had roles in films, including A Walk on the Moon, Amistad, Hurlyburly, She’s All That and Almost Famous as well as the English dub of Castle in the Sky.

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.

In 2009, Paquin played Irena Sendler, a Polish woman hailed as a heroine of the Holocaust, in The Courageous Heart of Irena Sendler, a CBS TV film biographical film based on the book Mother of the Children of the Holocaust: The Irena Sendler Story, by Anna Mieszkowska. The film was made in Latvia, and was a Hallmark Hall of Fame presentation for the network. In 2010, Paquin’s film The Romantics, a romantic comedy with Josh Duhamel and Katie Holmes, was released in the US at selected cinemas in September. She played a cameo role in Scream 4, alongside Kristen Bell in 2011. She also played the voice of Kristin on an episode of Phineas and Ferb.

On 5 August 2009, Paquin announced her engagement to her True Blood co-star Stephen Moyer, whom she had been dating since filming the series pilot in 2007. They married on 21 August 2010 at a private residence in Malibu, California. Paquin gave birth to fraternal twins in September 2012, and through her marriage to Moyer, she also has a step-son, Billy, born in 2000, and a step-daughter, born in 2002. The family resides in Venice, Los Angeles, California.

On 1 April 2010, Paquin came out as bisexual in a public service announcement for the Give a Damn campaign as part of the True Colors Fund, an advocacy group organised by Cyndi Lauper dedicated to LGBT equality. The True Colors Fund was created to “inspire and engage everyone, especially straight people, to become active participants in the advancement of gay, lesbian, bisexual and transgender equality”. The video features Anna Paquin stating, “I’m Anna Paquin. I’m bisexual, and I give a damn.” When asked about her participation in the video, Paquin responded by saying, “It wasn’t like it was a big secret, it was just a cause I cared about and privately supported, but not one that I had ever had an opportunity to speak out about in a way that would be useful. Obviously I know that one person’s voice doesn’t necessarily do that much, but I just wanted to do my bit.” In May 2012, in an Us Weekly interview Paquin rejected the notion that bisexuality is a choice. “My sexuality is not made up, for a bisexual, it’s not about gender. That’s not the deciding factor to who they’re attracted to,” stated Paquin. In 2014, she described herself on Twitter as “Proud to be a happily married bisexual mother”.

Paquin reprised her role as Rogue in the 2014 film X-Men: Days of Future Past, but most of her scenes were cut out for the theatrical release. An alternative version of the film with all of Paquin’s scenes reinstated was released as The Rogue Cut on 14 July 2015. Paquin voiced Ramsey in Disney•Pixar’s film The Good Dinosaur. She also played Nancy Holt, the wife of a Confederate soldier, in the 2016 miniseries Roots. In June 2016, the Human Rights Campaign released a video in tribute to the victims of the Orlando nightclub shooting; in the video, Paquin and others told the stories of the people killed there. Paquin starred in the Canadian crime drama Bellevue which airs on CBC Television and can next be seen in husband Stephen Moyer’s directorial debut, The Parting Glass.