Her first role was as Mary Crow Dog in the television production Lakota Woman: Siege at Wounded Knee, which depicted the 1970s standoff between police and Native Americans at Wounded Knee, South Dakota.
She is probably best known as the speaking voice of the titular character in the 1995 Disney animated feature Pocahontas and its direct-to-video sequel Pocahontas II: Journey to a New World. Bedard was also the physical model for the character. She appeared in a different take of the story in the 2005 film The New World, as Pocahontas's mother. Bedard attended The University of the Arts in Philadelphia, Pennsylvania, where she studied musical theatre.
In 2005, she was cast in the television mini-series Into the West, portraying the half-Lakota, half-white adult Margaret "Light Shines" Wheeler.
Irene Bedard is known for bringing a powerful emotional presence to her characters. She was chosen as one of People magazine 50 Most Beautiful People for 1995. She also played Nakooma in Squanto: A Warrior's Tale and voiced Forest Ranger Hero in Higglytown Heroes.