Inside the cockpit of a commercial airliner, pilots Tim Norton and Don Blake talk with insurance couriers Ben Edwards and Ed Davidson, who are carrying a shipment of $250,000. Norton walks to the back of the passenger cabin for some coffee, just as stewardess Marie Burke begins serving the passengers. Marie, a former racketeer whose real name is Connie Barrett, notices that two of her former accomplices, Andy Barrett and follies star Wanda LaFern, are among the passengers. When they accuse her of stealing $60,000 from them, Marie Denies it and begs them not to ruin her chance at a new life.
Minutes after drinking the coffee, everyone on board the plane falls asleep, including the crew. Passenger Lee Chan, travelling with his father, Charlie Chan, is the first to awaken. He notices a limp hand protruding from the cockpit door, and, upon closer inspection, discovers that Davidson has been stabbed to death and that the insurance money has been stolen.
After Lee awakens his father, he shows the detective the body of the victim. The plane’s crew is still asleep, and the airliner is cruising on automatic pilot. As his son takes the controls of the plane, Chan wakes everyone up and explains the situation. John Anderson introduces himself as an investigator for the insurance company that had been responsible for the lost money.
When the plane lands in San Francisco, police lieutenant Mike Ruark along with the owner of the insurance company, William E. French, question the passengers and crew, however, nothing of importance is revealed.
Later, at the Gayety Theatre, where Wanda LaFern performs her burlesque routine, Norton and Blake arrive backstage to see the follies star. Outside of Wanda’s dressing room door, Wanda is heard accusing Marie, her sister, of stealing the insurance money.
Meanwhile, Chan, Lee, Ruark, and Chan’s chauffeur Birmingham Brown arrive at the theater, where they find Blake, who lies unconscious with a badly fractured skull. When Ruark sees Norton running away, he arrests him, while Blake is rushed to a hospital.
Andy Barrett breaks into Chan’s home trying to talk with the detective. As he holds a gun on Chan, and is about to reveal something of importance, he is shot dead by Anderson, who had been following him.
Later, after going through the marriage records of several California counties, Chan and Lee discover the information that they have been seeking and go to the home of Jonathan Tibbetts, the justice of the peace who had officiated at the Barretts’ wedding years earlier. Barrett explains that he always takes photographs of the newlywed couples, and offers to look for the negatives of the Barrett wedding.
As Tibbetts enters his garage to look for the negatives, a shadowy figure knocks him out and lights the negatives on fire. Chan and Lee are alerted to the fire by Birmingham, who sees the smoke coming from the garage. After they rescue Tibbetts, he checks his order book noting that he had sent photos to the LaFern sisters, Connie and Wanda. Later, Chan and Lee locate a newspaper article about the LaFern sisters which includes a photograph of the pair, and they immediately recognize Connie as Marie Burke.
With Lt. Ruark’s help, Chan summons all of the remaining suspects back onto the plane. The detective then asks Connie, Wanda, and Tim Norton to take their places at the rear of the plane where the coffee was being served during the fateful flight, and where the three were standing just prior to the robbery.
After Chan tells everyone about the attack on Don Blake at the theater, he announces that Blake has recovered enough to identify the thief and murderer. A heavily bandaged Lee, impersonating Blake, boards the plane. As he raises his arm to point out the guilty individual, Connie grabs a gun from her purse. Before she can fire the weapon, however, Anderson shoots and kills her.
Chan then reveals that it was Anderson who had taken the money, secretly passing it to his accomplice French in the lining of his overcoat after the plane had landed. When Ruark tries to arrest them, French pulls a gun. With French covering everyone, Anderson, an experienced pilot, enters the cockpit, locks the door, and takes off. Shutting off the plane’s fuel, he exits the cockpit and locks the door, and, wearing the plane’s sole parachute on his back, he holds a gun on everyone, including French, and attempts to parachute from the plane. Realizing now that he has been double-crossed, French struggles with Anderson, and both are then grabbed by the police.
As Chan was prepared for this situation, he supplies an extra key to the cockpit door. After Norton opens the door and restores fuel to the plane’s engines, Norton hands over the controls to Lee who heads the plane back to the airport.