In the film, The Hunt for Red October (set in 1984,) Mancuso commanded the USS Dallas, a Los Angeles class nuclear submarine. Mancuso agreed to bring aboard CIA investigator Jack Ryan, who was operating on a hunch that Soviet captain Marko Ramius was attempting to defect to the United States in a secretly built nuclear submarine known as the Red October.
After the Soviet ambassador to the U.S, Andrei Lysenko, tricks the National Security Advisor Jeffrey Pelt into believing that Ramius had gone rogue and intended to fire the Red October's nuclear payload on Washington, Mancuso is ordered to intercept and destroy the Red October, much to the disbelief of Ryan. At the last second, Ryan convinces Mancuso that Ramius intended to defect by sending a message in Morse code with a spotlight.
Mancuso takes Ryan and Petty Officer Jones of the Dallas in the Dallas' emergency submersible to board the Red October after a U.S. frigate appears, acting on the same orders. Once there, the Red October's crew is attacked by a saboteur, who fatally wounds Red October's executive officer, Vasily Borodin, and attempts to kill Ramius. Ramius gives command of the Red October temporarily to Mancuso while Ramius hunts down the saboteur. A Soviet Alfa-class submarine, the V. K. Konovalov, which had been hunting the Red October since the submarine passed Murmansk, then catches up to the scene. Captain Tupolev of the Konovalov fires a homing torpedo at the Red October's engines, but thanks to some last minute maneuvering by Mancuso and Ramius, the homing torpedo is rerouted and destroys the Konovalov instead.
Mancuso returns to the Dallas while Red October is being towed to a port in Maine. This is the last appearance of Mancuso in the film.