George Kingsley, Stanley Ridges, is a bookish college professor who is accidentally run down by Red Cannon, a gangster fleeing from four former gang members bent on killing him. Red Cannon is crippled by the accident while Kingsley suffers life-threatening brain trauma. Boris Karloff as Dr. Ernest Sovac implants part of Cannon's brain into Kingsley to save his life. Cannon dies as a result, while Kingsley recovers but at times behaves like Cannon. Sovac is intrigued, not only because this suggests his procedure can preserve life indefinitely, but because Cannon has hidden $500,000 somewhere in New York City. Sovac persuades Kingsley to take a vacation in New York, ostensibly as a curative change of pace for his irritable mood; Sovac hopes this will revive Cannon's memory so that Kingsley will lead him to the fortune which he hopes to spend on a laboratory.
Sovac uses hypnosis to fully awaken the Cannon persona, which is accompanied by a change in physical appearance so dramatic that he becomes unrecognizable as either Kingsley or Cannon, and fills Cannon in on what happened since his accident. Cannon exploits the natural disguise of Kingsley's body to begin hunting down his former gang members and strangling them to death. Whenever he returns to the Kingsley persona, he has no memory of his doings as Cannon and is extremely tired. Police are baffled as to the identity of the "gangster killer", while his gang members assume he is an associate to whom Cannon passed on his knowledge before he died.
Margaret Kingsley, Virginia Brissac, and Sovac's daughter Jean, Anne Gwynne, concerned for Kingsley, come to New York. Jean recognizes Kingsley in his Cannon persona and draws an explanation out of Sovac. She entreats him to allow Kingsley to return home and recover. Sovac relents, promising to return Kingsley in the morning. That night Cannon goes to retrieve the stash. Sunny Rogers, Anne Nagel, Cannon's lover, alerts the remaining gang members, who follow him to the stash to take it from him.
Cannon fights them off and strangles them, along with Sunny. Cannon reverts to the Kingsley persona and returns to Sovac with the box, not knowing it contains Cannon's fortune.
Upon returning home Kingsley returns to normal, the Cannon persona no longer manifesting even as the earlier fits of irritability. However, while Kingsley is teaching a class, a police siren reawakens the Cannon persona. Cannon heads to the Sovac home in search of the money and attempts to murder Jean. Sovac shoots him dead.
Sovac is executed for murdering Kingsley. Before stepping into the electric chair he gives notes on his brain transplant procedure to a reporter, in the hopes that his work may one day be put to better use.