Off the coast of Alaska, oceanographer Emma MacNeil (Deborah Gibson) is studying the migration patterns of whales aboard an experimental submarine she took without permission from her employer. Meanwhile, a military helicopter drops experimental sonar transmitters into the water, causing a pod of whales to go out of control and start ramming a nearby glacier. In the chaos, the helicopter crashes into the glacier, and the combined damage breaks the glacier open, thawing two hibernating, prehistoric creatures. Emma narrowly avoids destruction as, unknown to her, a giant shark and octopus are freed.Some time later, a drilling platform off the coast of Japan is attacked by the octopus, which has tentacles large enough to wrap around the entire structure.After returning to Point Dume, California, Emma investigates the corpse of a beached whale covered with many bloody wounds. Her employer Dick Richie (Mark Hengst) believes them to be from a tanker propeller, but MacNeil insists they appear to be from a creature. Later, she extracts what appears to be a shark's tooth from one of the wounds. Elsewhere, the huge shark leaps tens of thousands of feet into the air from the ocean and attacks a commercial aircraft, forcing it to crash into the water.A review board convenes and fires Emma (on the advice from Dick Richie) from the oceanographic institute for stealing the submarine. She goes to her home and brings the shark tooth to her old professor, former U.S. Navy pilot Lamar Sanders (Sean Lawlor), who believes it belonged to a Megalodon, an enormous species of shark believed to have become extinct 1.5 million years ago. The duo is visited by Dr. Seiji Shimada (Vic Chao), a Japanese scientist trying to determine what attacked the drilling platform. The three review a videotape recorded during Emma's submarine voyage, finding images of both the megalodon and a gigantic octopus. Emma reflects on the polar ice caps melting due to man-made global warming, and wonders if the creatures are mankind's "comeuppance". Meanwhile, a U.S. "naval destroyer" engages the megalodon, but is destroyed after its guns fail to destroy the shark.Emma, Sanders, and Shimada are arrested by a team of soldiers and taken to government official Allan Baxter (Lorenzo Lamas), a rude and racist man who demands their help in destroying the creatures. The three agree to help, in exchange for the government trying to capture the creatures for study rather than destroy them.While working at a naval laboratory to develop a method for luring the creatures, Emma and Shimada become attracted to each other and have sex in a utility closet. The incident makes them realize they can attract the creatures using chemicals. Emma and Sanders agree to place a trap for the shark in San Francisco Bay, while Shimada returns to Tokyo to attract the octopus. Emma and Sanders barely escape the shark after placing the trap with a mini-submarine. The plan fails, however, when the shark destroys another destroyer sent by Baxter. The shark then resurfaces and bites off a large portion of the Golden Gate Bridge, killing many civilians on the bridge.Later, Shimada contacts the Americans and says the Japanese trap, having the same disaster, only succeeded in angering the octopus, which has escaped despite multiple artillery and missile hits. Baxter suggests using nuclear weapons against the creatures, which Emma, Sanders, and Shimada strongly oppose due to the risk of marine devastation, coastal damage and human casualties. As an alternative, Emma suggests using the same pheromone traps to create a "Thrilla in Manila" by drawing the two creatures together. She believes that because the two creatures were frozen in ice locked in combat, they must be natural rivals and their aggressiveness towards one another will cause them to fight to the death if they're lured together. Emma, Sanders, and Baxter are assigned to a submarine to find the shark and lure it to the North Pacific Ocean.After a short search, the submarine brings both the shark and the octopus to an ice trench off the Alaskan coast, where Emma first encountered the creatures. Sanders himself ends up piloting the sub after the original pilot loses his nerve and pulls a gun on the captain (Dean Kreyling) before he is overtaken. The octopus and shark begin to fight, Giant Octopus, wraps around Mega Shark, and tries to suffocate him. Mega Shark bites the tentacles to get free. They separate. Mega Shark attacks the submarine. dragging it in its mouth. Emma, Sanders, and Baxter man a mini-submarine and detach just as the shark bites the larger submarine in half, killing the rest of the crew. The shark nearly destroys the mini-submarine, but they are saved when a Japanese sub with Shimada on board fires torpedoes at it. The octopus entangles the Japanese submarine and nearly destroys it, but the sub is released after the octopus is attacked by the shark.The two sea creatures engage in a fierce battle, at the end of which, the octopus strangles the shark after the shark dismembers some of its tentacles, causing it to bleed to death. The two sink, dead, still locked from their battle. Emma and the others, after watching the showdown between the two monsters, discover Shimada and his sub survived the octopus attack. The film ends with Emma, Sanders, and Shimada deciding to visit the North Sea after receiving infrared images of mysterious organic life there.