Emily Hampshire is most widely known to international audiences for her role as Angelina to Sean Astin's Michael in the 1998 romantic comedy Boy Meets Girl, and Vivienne in the 2006 film Snow Cake, in which she starred opposite Sigourney Weaver and Alan Rickman. Having been professionally active in the Canadian film and TV industry since 1996, Hampshire is also notable for her role as Siobhan Roy on Made in Canada. More recently, she has starred in the Canadian series This Space For Rent, Carl and Northern Town. She also starred alongside Kevin Zegers and Samaire Armstrong in the 2006 romantic comedy It's a Boy/Girl Thing, in which she played the character Chanel. She played Margaret in The Life Before This, a feature film directed by Jerry Ciccoritti, which premiered at the Toronto International Film Festival in 1999. She also voiced Starr/Nebula on the animated Canadian sitcom 6Teen. Most recently, she appeared in The Trotsky as Leon Trotsky's love interest Alexandra; in the Canadian indie film, Good Neighbours as Louise; and in David Cronenberg's Cosmopolis as Jane Melman.
Hampshire has also done voice-acting, voicing the character Misery on the animated series Ruby Gloom, Diana Barry in Anne of Green Gables: The Animated Series, Chloe Crashman in Carl Squared, Starr in 6Teen, and Alyson Malitski in Braceface. On 23 May 2012 in Cannes, France, Birks presented the first Birks Canadian Diamond award to Hampshire and fellow actress Sarah Gadon during Telefilm Canada's inaugural Tribute To Canadian Talent press event and reception. Also in 2012, Hampshire co-starred in Sean Garrity's comedy film My Awkward Sexual Adventure for which she received positive critical notice. The same year she was cast in the futuristic-zombie film The Returned. In 2014 Hampshire was cast in the Syfy series 12 Monkeys in the recurring role of Jennifer Goines, a reimagined version of Brad Pitt's character from the film on which the series is based; in 2015, she was upped to a series regular for the show's second season. She also plays Stevie Budd on CBC Television's Schitt's Creek. In late 2015, Hampshire was cast in Xavier Dolan's independent film The Death and Life of John F. Donovan, which also stars Jessica Chastain, Kathy Bates, and Susan Sarandon.