Byrnes was born in St. Louis, Missouri. His mother was a homemaker, and his father was a municipal accountant. In 1968 he was drafted and served in the Vietnam War for a year in the 196th Infantry Brigade. He has lived in Vancouver, British Columbia, Canada, since the mid-1970s. On February 26, 1972, he was struck by a passing car while he attempted to help move a stalled truck on the Island Highway North of Parksville, which injured his legs and forced them both to be amputated.
Fifteen years to the day after the accident, he started appearing on Wiseguy as Daniel Burroughs, better known as Lifeguard. It was his first major role and lasted until 1990. Later, he starred in the fantasy television series Highlander: The Series as Joe Dawson, a member of a secret society known as the "Watchers." He reprised his role as Joe Dawson in Highlander: Endgame and Highlander: The Source, later installments of the Highlander film series, as well as providing voices for the anime Highlander: The Search for Vengeance. He starred in his own short-lived TV show, called The Jim Byrnes Show. He played a recruiting sergeant for the Union Army in an episode of "Copper" called "The Children of the Battlefield."
His other television roles include Higher Ground and cartoon voices in Beast Wars: Transformers, Beast Machines: Transformers, Shadow Raiders, Stargate Infinity, Dinosaur Train as Percy Paramacellodus, Colonel Nick Fury in X-Men: Evolution and as Duke Dermail in Gundam Wing. He appeared in the Taken mini series, which broadcast on the Sci-Fi Channel and an episode of Twilight Zone entitled "Harsh Mistress". He has also appeared on the Syfy series Sanctuary, appearing as the father of Helen Magnus, played by Amanda Tapping and as Shineoa San in an episode of Andromeda as well as the voice of Virgil Vox in nine additional episodes.
As a musician, Byrnes has won the Juno Award for Blues Album of the Year three times, for That River in 1996 and House of Refuge on Black Hen Music in 2007, and for Everywhere West in 2011. Byrnes was also honoured at the 2006 Maple Blues Awards, as Male Vocalist of the Year. The Canadian Folk Music Awards recognized him as the Contemporary Singer of the Year in 2006 and 2009.