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.
When Sach eats too much sugar, he goes into a trance whereby he's able to predict the future. Slip tries to make some money off of Sach by using him as a fortune teller in a carnival, until a mad scientist kidnaps Sach to use him in an intelligence-switching experiment with a monster.
Slip and Sach take the rap for a robbery they did not commit in order to uncover the real robbers, whom they suspect are led by a convict who gives orders to his gang outside via a short-wave radio stashed somewhere in the prison.
An overambitious shutterbug almost gets his lights put out permanently when he decides to snap a picture of a mob boss.
Sach receives news that he is the heir to the Terwilliger Debussy Jones fortune. Accompanied by his pal Slip, he arrives at the Jones mansion to review the legal papers needed for him to claim his new fortune. However, Sach and Slip discover that the rightful heir, the young Terwilliger III, is being cheated out his inheritance by the miscreant duo of Stuyvesant Jones and Clarissa. Sach and Slip, with the help of their fellow Bowery Boys, save the day and restore the heir’s inheritance.
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.
An electric shock enables Satch to predict numbers, so the Bowery Boys are off to Las Vegas to win enough money at the roulette wheels to let their landlady buy an apartment building. Witnessing his winning streak, some gangsters decide to move in and find out his "system" for beating the odds.
Slip and Sach's boss, David J. Thurston, has allegedly committed suicide. Slip finds a book of matches with the name of a local nightclub on his boss' desk and finds out from Gabe that a gambling casino is being run out of it. Slip comes to the conclusion that the club had something to do with his boss' death and sets out to find his murderer. The boys get jobs at the club and Louie poses as a rich cattlemen as they gather the information to convict the murderers.
Sach and the gang baby-sit a bratty TV star.
The Bowery Boys are enrolled in a fancy college by a pair of rich snobs who think they can turn the Boys into classy guys. Sach becomes a football star, and is kidnapped by gangsters to keep him out of the big game.
When a cold medicine causes Sach to be able to smell diamonds, he and the rest of the Bowery Boys are induced by a diamond dealer to accompany him to Darkest Africa in search of a legendary cache of them.
A ghost helps the Bowery Boys capture a gang of crooks led by a mad doctor.
The boys are working at the local boxing arena where their friend, Jimmy Higgins, is boxing. During a crooked match Jimmy is killed. The boys seek out his older brother, Johnny, a former boxer who gave up the sport rather than go crooked, and help train him to get back in the ring. They try to get him a shot at the title, and when they do the same crooked gangsters that were behind Jimmy's death try to get Johnny to take a dive.
The Bowery Boys take on British crooks when one of them thinks he's inherited a title.
Sach is given a post-hypnotic suggestion that turns him into a championship prizefighter.
Slip, Sach and the rest of the Bowery Boys enter a haunted house, where they engage in slapstick with a gorilla, a robot and a vampire
While Louie is on vacation, the boys turn The Sweet Shop into an escort service, and soon find a group of beautiful girls as their first clients.
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.
Slip and Sach are in the sidewalk star-gazing business when they see a murder committed in a room at the El Royale Hotel.
The Bowery Boys join the Navy to catch some crooks who are posing as sailors.