Chris Eyre was born in Portland, Oregon, to a Native American mother, then given up for adoption. Raised by Caucasian parents, Eyre eventually reconnected with his biological mother and the rest of his extended Native family, who live throughout the American West.

While studying at New York University's film school, Eyre wrote and directed the Indian drama Tenacity, which won NYU's Best Short Film and a place at the 1995 Sundance Film Festival. That same year, he was invited to the Sundance Directing Workshop to work under the tutelage of Robert Redford and Steven Zaillian on a short screen adaptation of Sherman Alexie's screenplay, Someone Kept Saying Pow Wow, which he later made into the feature film Smoke Signals in just 23 days. After the film's debut at the Sundance Film Festival, where it garnered the coveted Audience Award and Filmmaker's Trophy, Smoke Signals was released to critical acclaim by Miramax. Eyre is currently developing a screen adaptation of Peter Matthiessen's best selling book The Spirit of Crazy Horse, about American Indian activist Leonard Peltier.