The Vipers, a band of outlaws, have been pulling off raids across Kansas towns. A clue leads West and Gordon to the quiet village of Freedom, where they meet a straight-shooting sheriff and a mayor who will stop at seemingly nothing to become governor. Gordon goes undercover and finds the plans to the Vipers' get-away wagon, while West discovers the secret entrance to the outlaws meeting place.
During Mardi Gras in New Orleans, agents West and Gordon look for the cruelest former commander of a Civil War prison who has been a fugitive from justice for the abuse of prisoners. They meet a young girl who leads them to Hazard, her legless father and victim of the prison commander. Hazard and his men are after the commander as well, but their real goal is to find a shipment of one million dollars that disappeared after arriving at the prison.
Revenge, jealousy and a rivalry between two doctors result in dastardly human experiments when James West comes upon a voodoo sacrificial killing. As West shoots his gun into the air to stop the ritual, the zombie-like participants turn and walk away. West is then attacked by a huge man named Tiny John, but as the agent shoots the man in the heart, Tiny John simply turns away and heads for the swamp. While the agents investigate further, they learn why the people are in a trance and discover the real reason behind the doctors' contempt for each other.
Special agent West is charged with the responsibility to transport the state's only supply of a smallpox vaccine to safety. On the way, West's stagecoach is ambushed by a gang, led by Silas Crotty, who steals the serum and shoots West as he tries to protect the vaccine. When West awakens in the field, he has lost his memory and his identity.
While President Grant attends a fencing contest at the German consulate, he is invited by Baron Hinterstoisser to a reception and special presentation afterward. Agent West learns that the Baron plans to show a bogus kinetoscope film (see Goofs) revealing Grant signing a secret agreement with a nation of questionable character. Because an embassy is considered protected foreign soil, West and Gordon need to disrupt the Baron's plot by substituting their own fake film without being discovered, thereby causing an international incident.
A religious fanatic (played by Ted Knight) warns passersby at the San Francisco harbor that the city will be destroyed because of its citizens' wild ways. When a kraken (a sea monster) attacks at a pier, West tears off a piece of its tail, which is man-made. Gordon investigates by going undercover as an old salt, while West works with the U.S. Navy.
A priceless ruby is stolen from an Egyptian exhibit at the San Franciso Museum. When West and Gordon are commissioned to recover the jewel, they led to a waterfront bar where they notice the ruby on the toe of a beautiful young woman dancing on the table. Gordon, disguised as a sea captain, chases the dancer but fails to capture her or the ruby. As West gets closer to the dancer, he discovers that he has competition from two other unsavory characters who will stop at noting to get their hands on the valuable gem.
While West gets a shave at the barbershop, he becomes anesthetized by a hot towel and awakens in a fun-house. West soon learns of a series of kidnappings with clues leading to a traveling circus. There, West encounters the demented Dr. Miguelito Loveless with his latest invention, a powerful mechanized man. After the mechanical man knocks out West, places him in a coffin and throws the agent into a river, Loveless plans to hold a mock trial for his abducted victims and sentence them to death.
West and his temporary partner Jeremy Pike investigate a Chinese gangster's theft of rare explosives from a San Francisco armory. Artemus Gordon (Martin) is said to be on desk duty in Washington. The dying words of a murdered Chinese informant, leads Pike to go undercover in China Town searching for the thief, while West masquerades as a military prisoner at forbidding Ft. Alcatraz.