Santo vs. The Terror Riders aka Santo contra los jinetes del terror sees a small group of lepers, led by José, escape from a sanatorium run by Dr. Ramos. They rob several nearby farms, terrorizing the settlers, who demand that local lawman Darío do something. One of the biggest complainers is Camerino. However, Camerino actually has approached the lepers and offers to give them food, drink, and half of the booty if they help his gang carry out various robberies.
Darío calls on El Santo, famous crime fighter, to lend a hand. They set several traps for the criminals, but the gang always escapes. After one raid, José stops by the ranch where Lupe, his former girlfriend, lives. She says she has always been faithful to him, and José sadly tells her goodbye forever.
After another raid, Camerino kidnaps Carmen, Darío’s girlfriend. The townspeople plan to attack the sanatorium and kill the other lepers, but Darío convinces them to wait until the next day. Santo discovers the gang’s hideout: he defeats the crooks, and frees the lepers. Camerino is shot trying to escape. Santo tells the lepers that a new drug has been discovered which will allow them to lead normal lives; he then leaves town, to the cheers of the grateful populace.