Geronimo's curse has touched a quiet frontier town, turning some residents into zombies and setting off a chaotic, darkly comic chase through the streets and saloons. In this unsettling mix of Western and horror, Ben Goodman, a man in a house near the edge of town, behaves suspiciously and then attacks and eats his wife and daughter's brains, signaling that the curse has arrived in full force. Luke, [Chris Kattan], a cowboy planning to marry a saloon girl, rides into town to propose at the local saloon and quickly discovers Elmer Winslow, [James Denton], who has just arrived and learns that his “princess” is a prostitute. A tense confrontation explodes into a fight, and Sheriff Claypool, [Matt Besser], who owns the saloon, steps in to arrest them and ends up stealing Elmer’s $500. In the adjacent cell sits Deputy Cletus, [Chris Coppola], awaiting his fate, while Ben’s presence in the town becomes increasingly ominous.
Luke and Elmer manage to escape, locking Cletus in the cell, where he is bitten by Ben. They locate the sheriff and the prostitute, swipe the sheriff’s money, and make a quick getaway. The next morning, the town hangs Ben and forms a posse to chase the two fugitives. The tension spikes when Sue, Geronimo’s niece, [Navi Rawat], who was kidnapped and taken to New York to be educated, ambushes them in their sleep to exact revenge on the soldiers who killed her uncle. After a rocky start, Luke, Elmer, and Sue form an uneasy alliance, even as Elmer reveals he is an army deserter.
As the posse marches on, the sheriff and Cletus—now undead—attack the remaining posse members, turning more townspeople into zombies. The trio—Luke, Elmer, and Sue—realize they cannot be killed in the ordinary way and manage to keep ahead. Meanwhile, the townspeople cut Ben down from the gallows, not understanding that hanging won’t stop him. Padre, the town’s minister, [Leslie Jordan], escapes by locking himself in an upstairs room at the saloon, which is now besieged by the zombie horde. He climbs out a window to fetch water but is pursued and bitten by the prostitute.
The trio is captured by soldiers—Elmer’s former colleagues—at a fort on the edge of the Grand Canyon. They discover the posse arrived first and turned the fort’s garrison into zombies, who then attack the group and turn more soldiers. They learn that decapitation can kill the zombies. During a tense night in the fort, Sue explains that the only cure for the zombie curse is to eat the living flesh of the medicine man who created it. An improvised plan explodes as Elmer tries to punch First Sergeant Kermit, [Todd Anderson], and ends up bitten by him; after a clutch sequence involving the fort’s magazine, Elmer is transformed into a zombie and hurls Cletus off a cliff, then bites Luke. Sue manages to kill Sheriff Claypool, but she is soon attacked by Elmer and Luke.
In the aftermath, Elmer and Luke appear normal again—having eaten Sue’s flesh, which the story treats as the cure—and it seems the remedy also works for relatives of the man who created the curse. Sue, who tasted like gingerbread, is no longer a threat to them, and the two ride off toward the sunset as Cletus staggers to his feet and gives chase. An epilogue revisits Ben digging up his now-zombie family from the cemetery, and the three of them—with their loyal dog—skip back into town, leaving the audience with a final, eerie wink at the town’s perpetual undead.
