After Slip is drafted into the Marines, the rest of the gang volunteers so they can be with him. Sach discovers that the colonel knew his father and he is promoted. During a drill that he is putting the rest of the gang through, they find a soldier left for dead on the side of the road. Slip discovers a playing card next to the marine and traces it to Jolly Joe Johnson's gambling house. They suspect that the gambling house is cheating and set out to uncover the proof.
Dr. Tom O'Hara takes over a public clinic in New York's desperately poor Bowery section. Boy gangleader Sock Dolan resents Tom's interference in moving Sock's kid brother to a hospital, because Sock blames hospitals for his mother's death. Sock helps racketeer J.R. Mason sell food to the clinic, unaware that Mason sells cheap and often tainted food. When a number of patients, including Sock's brother, become ill from food poisoning, Sock is kidnapped by Mason to keep him silent. Dr. O'Hara must find a way to rescue Sock and stop Mason's contamination of hospital food supplies.
Slip invites his cousin Jimmy to stay with his family after he is released from prison. However, Jimmy soon gets mixed up with an auto-theft ring.
The Bowery Boys: In order to be able to get the names of winning horses at the track, Sach agrees to sell his soul to the devil.
Slip (Leo Gorcey), Sach (Huntz Hall), Bobby (Bobby Jordan), Whitey (William Benedict) and Chuck (David Gorcey) unsuccessfully try to sell a dilapidated car to a street cleaner for a fabulous amount, so they can get enough money to save Louie's (Bernard Gorcey) Malt Shop. Sidewalk photographer Cathy Smith (Teala Loring) snaps a pictures of three bank robbers as they are fleeing a robbery but when the Bowery Boys and Cathy realize that Sach is also in the photograph, they break into the photo lab to destroy the negative, which might make the police think Sach was involved in the robbery.
The Bowery Boys-Slip, Sach, Bobby, Whitey & Chuck-start their own exterminating service, and get a job which takes them to a spooky old abandoned mansion in the middle of the night. Meeting up with pal Gabe and his new French bride, the boys are tormented by mad scientists who try to convince them the place is haunted and then kidnap Sach in order to place his brain inside a gorilla.
A man wins $50,000 in a card game with gamblers, but is soon found dead and the money missing. Slip and Sach find the money near where the body was discovered, and soon find themselves the target of both the police and the gamblers.
Slip and Sach are working for a local newspaper as a reporter and photographer, respectively. Slip wants to get the goods on a local gambling ring that is fixing sporting events, so he and Sach go undercover to expose the ring.
The Bowery Boys head west to clear Louie of an old murder charge that he had killed his gold-mine partner. Sach has the map to the gold mine painted on his back, and Blackjack McCoy has him kidnapped by Indian Joe. Gabe poses as a dangerous gunman, the Klondike Kid, while Slip is in charge of all the remaining loose ends.