Katharine Isabelle was born on November 2, 1981 in Vancouver, British Columbia. She is the daughter of Graeme and Gail Murray. Graeme Murray is an art Director and production designer who has won two Emmy Awards for his special effects work on the television series The X-Files. Her mother, Gail Murray, is an amateur Vancouver Writer and Producer. Katharine is the sister of Journalist and former child actor, Joshua Murray.
In 1989, Isabelle broke into acting with parts in the films Cousins, Cold Front, and an episode of MacGyver. In 1992, she played the role of Erica Sanderson in Knight Moves. American audiences took notice of her performance as Lindsay Clark in the teen thriller, Disturbing Behavior (1998).
Isabelle has appeared in numerous television series throughout her career, including The X-Files (1998), Da Vinci's Inquest (1998), Smallville (2003), and Supernatural (2007).
Throughout the 2000s, Isabelle appeared in several horror and slasher films, including Freddy vs. Jason (2003), Ginger Snaps 2: Unleashed (2004), Spooky House (2004), Ginger Snaps Back: The Beginning (2004), Rampage (2009), and Hard Ride to Hell (2010).
Isabelle also appeared in several independent films, including Falling Angels (2003), On the Corner (2003), The Last Casino (2004), Everything's Gone Green (2006), the short film Favourite People List (2009), and Frankie and Alice (2010).
In 2008, Isabelle received the Gemini Award for Best Performance by an Actress in a Featured Supporting Role in a Dramatic Program or Mini-Series for her role in the critically acclaimed The Englishman's Boy.
In 2012, Isabelle starred in the popular horror film American Mary, which earned her special mention at the Austin Fantastic Fest, Festival Trophy Award for Best Actress, Special Award for Best Actress, Fright Meter Award for Best Actress, and Fangoria Chainsaw Award for Best Leading Actress. More recently she has appeared in 13 Eerie (2013), Torment (2013), and Laurence & Holloman (2013) which earned her a Leo Award nomination for Best Supporting Performance by a Female in a Motion Picture. In 2014, she starred in See No Evil 2.
She portrayed Margot Verger in the second and third seasons of the NBC TV series Hannibal (2014–15). In 2015, Isabelle starred in the thriller film 88 and the horror film The Girl in the Photographs. That year she starred in the indie film How to Plan an Orgy in a Small Town alongside Jewel Staite, Lauren Lee Smith, and Ennis Esmer.