Michael Lanyard, better known as the Lone Wolf, and his loyal Jamison spot a cat wearing a pearl necklace one night in New York City. Their pursuit leads them to a bank, where a trap snaps shut around them, and Inspector Crane arrives hot on the trail of the mysterious thief. The cat’s sudden appearance deflates Crane’s victory, but he still taunts Lanyard with a snappy bet: he will pay two months’ salary if Lanyard can stay out of trouble for 24 hours.
Lanyard checks in at the same hotel as the glamorous Gloria Foster, a movie star who becomes entangled in the night’s schemes. Her fiancé, Johnny Baker, has just sent a telegram claiming Gloria has information about his invention. Baker is wary but determined, and a former private detective, Wallace, waits nearby in the hallway. What unfolds is a trap: two men seize Baker and haul him away under the cover of darkness. Wallace climbs onto a narrow ledge to reach the room, banging on Lanyard’s bathroom window for help. Lanyard, misreading the situation, thinks Wallace is still working with Crane. A crook fires, Wallace falls to his death, and the pull cord from Lanyard’s room is ripped away along with him. Lanyard realizes the danger and orders Jamison to tail the fleeing trio, while he discovers a discarded telegram and Crane, arriving later, suspects Lanyard of Wallace’s murder because the cord is missing.
Seeking truth, Lanyard visits Gloria Foster. While he waits, a newsreel reveals that Baker’s invention—a “burglar-proof” government mail car—will carry currency engraving plates to San Francisco on its maiden trip, and that Baker alone knows the combination. The revelation shifts the chase: Jamison shadowing the crooks leads to the station, where the formidable plan intensifies. Frank Jordan, a henchman, and Johnny (on a stretcher) board the train carrying the priceless cargo, while ailing “Dr.” Hooper Tupman is wheeled into the picture and the stakes climb higher. The entourage moves to guard the criminal operation, and Foster is taken by the thieves, with Evelyn Jordan stepping in to complicate the scene.
Crane moments later takes custody of Lanyard and Jamison, but Lanyard insists that Foster can clear his name; however, Evelyn Jordan answers the door, and the robbers slip away with the plates. The pair escape, stealing a taxi and pursuing the thieves’ ambulance. A desperate chase ends in a ditch, forcing Lanyard and Jamison to press on on foot. They rescue Gloria Foster from an abandoned house, and she is sent to the authorities while Lanyard continues the search for the missing plates. Crane shows up with Sheriff Haggerty, but Lanyard still eludes capture. He discovers a hidden door to the crooks’ lair and is knocked out as the robbers escape with the plates.
Tupman hides the plates by lowering them down a well, and the thieves speed away with the precious cargo. Lanyard and Jamison repair their ambulance and press on with a renewed plan to recover the prize. The trail leads to a theatre showing the latest newsreels, where Lanyard spots Baker on screen and can finally read the combination in a magnified frame. With time running out, they overtake the train by chartered airplane and seize control just as the police close in. Lanyard sets a stop signal, boards the car, and rescues Baker just as the guards break in and trigger a release of poison gas.
In a climactic pursuit across the Midwest, Lanyard corners the thieves, outsmarts their scheme, and saves the day by securing the mail car’s contents. The mission is accomplished, justice is served, and the notorious “Lone Wolf” proves once again that cunning, nerve, and a sharp eye for detail can outpace even a well-planned heist.