Hired by local robber barons, Harvard Law Graduate Brisco County, Jr. searches for the members of the infamous John Bly gang, the same men who killed his father, a famous marshal and western legend. Accompanied by his one-time rival and fellow bounty hunter Lord Bowler, Brisco rides through the West trying to bring his father's killers to justice. Along the way, he encounters mysterious golden orbs with strange abilities and colorful characters who help or hinder his mission as he hunts down the Bly gang one by one.

Brisco's horse was billed in the credits as "Comet the Wonder Horse," and named Comet in the show, with the implication that he was the smartest character on the show. In fact, "Comet" was actually portrayed by four separate horses, with the horse being used in any particular scene depending on the type of action Comet was expected to perform.

Brisco County Jr.:
If I was gonna kill you, I'd be stepping over your body right now on my way out the door.