At the end of the street is a dock on the East River; to the left are the luxury apartments and to the right are the slums. The Dead End Kids, led by Tommy Gordon (Billy Halop), are a petty gang of street urchins who are already well onto a path to a life of crime. Members of the gang besides Tommy include, Dippy (Huntz Hall), Angel (Bobby Jordan), Spit (Leo Gorcey), T.B. (Gabriel Dell), and Milty (Bernard Punsly), the new kid on the block in search of friends. Spit is a bit malicious with a cruel streak and initially bullies the newcomer and takes his pocket change. However, Tommy eventually lets Milty join the gang and turns out to be both a loyal and generous friend.
Tommy's sister, Drina (Sylvia Sidney), dreams of marrying some dashing, rich stranger who will save her and Tommy from this miserable life of poverty and help prevent Tommy from growing up to be a mobster like Baby Face Martin (Humphrey Bogart), who has returned to the neighborhood to visit his mother and old girlfriend. Drina's friend, Dave Connell (Joel McCrea), is an unemployed architect who currently works odd jobs. He is having an affair with a rich man's mistress, Kay Burton (Wendy Barrie). Although Dave and Kay love each other, they know they can't be together because Dave cannot provide Kay with the lifestyle she desires.
Meanwhile, the kids rough up a rich kid (Charles Peck) who lives in the apartments. When the boy's father tries to intervene, Tommy winds up stabbing him in the hand. He escapes the police and goes into hiding.
Martin, meanwhile, is rejected by his mother (Marjorie Main) and repulsed by his ex-girlfriend, Francie (Claire Trevor), who is now a prostitute. Despondent over the failed visit, he decides to kidnap the rich child for ransom to make the trip back worthwhile. Dave tracks Martin down and kills him after a struggle. When the police arrive, a crowd gathers, including Spit, who is recognized as being a member of the gang that attacked the rich man. He exonerates himself by informing the police that it was Tommy who stabbed the man. Tommy hears of Spit's betrayal and tries to give him the mark of the "squealer", which is a knife wound across the cheek. Before he can do so, Dave apprehends him and convinces him to turn himself in. He agrees to use his reward money from Martin's slaying to pay for Tommy's defense.
Writing in the New York Times, Carter B. Horsley said of the River House: "Erected in 1931 when its area still teemed with tenements, it was mocked in the famous and popular 1936 movie, 'Dead End' that was Lillian Hellman's adaptation of Sidney Kingsley's play.