John Wayne is not the title character of Flame of the Barbary Coast: that honor goes to second-billed Ann Dvorak. Wayne plays a Montana cattleman who is lured into a San Francisco gambling joint by dance-hall girl Dvorak. Though Ann at first brings Wayne luck, he ends up losing his shirt to cardshark Joseph Schildkraut. Chastened by the experience, Wayne leaves Frisco with his tail between his legs, returning only after he himself has become a gambling expert. Thanks to his new-found expertise, Wayne is able to rake in enough bucks to open his own saloon, bringing Dvorak along for the ride as star of the floor show. Numerous intrigues ensue, culminating in a drawn-out trial scene. As the judge is about to reach a decision, the San Francisco Earthquake strikes (mostly off-screen, drat the luck). When Dvorak is injured in the disaster, Wayne is forced to realign his values. The Duke and The Dvorak decide to bid adieu to the City by the Bay, heading off to Montana to start life anew.