Far north of the Arctic Circle, a nuclear bomb test, dubbed Operation Experiment, is conducted. Prophetically, right after the blast, physicist Thomas Nesbitt (Paul Christian) muses, "What the cumulative effects of all these atomic explosions and tests will be, only time will tell." Sure enough, the explosion awakens a 10-metre (33 ft) tall, 30-metre (98 ft) long carnivorous diapsid known as the Rhedosaurus, thawing it out of the ice where it had been hibernating for 100 million years. The only witness to the beast's awakening, Tom Nesbitt, is dismissed as delirious, but he persists.
The Beast starts making its way down the east coast of North America, sinking a fishing ketch off the Grand Banks, destroying another near Marquette, Canada, wrecking a lighthouse in Maine, and crushing buildings in Massachusetts. Nesbitt gains allies in paleontologist Thurgood Elson (Cecil Kellaway) and his lovely young assistant Lee Hunter (Paula Raymond) after one of the surviving fishermen identifies from a collection of drawings the same dinosaur as Nesbitt saw. Plotting the sightings of the Beast on a map for skeptical military officers, Elson proposes the Beast is returning to the Hudson River area where fossils of Rhedosaurus were first found. In a diving bell search of the undersea Hudson River Canyon, Professor Elson is killed by the Beast. The Beast eventually comes ashore in Manhattan. A newspaper report of the Beast's rampage lists "180 known dead, 1500 injured, damage estimates $300 million".
Arriving on the scene, military troops led by Col. Jack Evans (Kenneth Tobey) stop the Beast with an electrified barricade, blast a bazooka hole in the Beast's throat and drive it back into the sea. Unfortunately, it bleeds all over the streets, unleashing a "horrible, virulent" prehistoric germ, which begins to contaminate the populace, causing even more fatalities. The germ precludes blowing the Beast up or burning it, lest the contagion spread. Thus it is decided to shoot a radioactive isotope into the Beast's neck wound with hopes of burning the Rhedosaurus up from the inside, killing it.
When the Beast comes ashore and attacks the Coney Island amusement park, military sharpshooter Corporal Stone (Lee Van Cleef) takes a rifle grenade loaded with a potent radioactive isotope, (the only one of its kind outside of Oak Ridge, so pressure is on him not to miss), and climbs on board a rollercoaster. Riding the coaster to the top of the tracks so he can get to eye-level with the Rhedosaurus, he fires the isotope into the Beast's wound. The Beast lets out a horrible scream, thrashes about setting the park ablaze and finally crashes to the ground in its death throes.
- Paul Christian as Professor Tom Nesbitt
- Paula Raymond as Lee Hunter
- Cecil Kellaway as Dr. Thurgood Elson
- Kenneth Tobey as Colonel Jack Evans
- Donald Woods as Captain Phil Jackson
- Ross Elliott as George Ritchie
- Steve Brodie as Sgt. Loomis
- Jack Pennick as Jacob Bowman
- Michael Fox as ER doctor
- Lee Van Cleef as Corporal Jason Stone
- Frank Ferguson as Dr. Morton
- King Donovan as Dr. Ingersoll
- James Best as Charlie, radar operator