Back when the Earth was being overrun by glaciers, and animals were scurrying to save themselves from the upcoming Ice Age, a sloth named Sid, a woolly mammoth named Manny, and a saber-toothed tiger named Diego are forced to become unlikely heroes. The three reluctantly come together when they have to return a human child to its father while braving the deadly elements of the impending Ice Age.

Manny the woolly mammoth, Sid the sloth, Diego the saber-toothed tiger, and the hapless prehistoric squirrel/rat known as Scrat are still together and enjoying the perks of their now melting world. Manny may be ready to start a family, but nobody has seen another mammoth for a long time; Manny thinks he may be the last one. That is, until he miraculously finds Ellie, the only female mammoth left in the world. Their only problems: They can't stand each other--and Ellie somehow thinks she's a possum! Ellie comes with some excess baggage in the form of her two possum "brothers"-- Crash and Eddie, a couple of daredevil pranksters and cocky, loud-mouthed troublemakers. Manny, Sid and Diego quickly learn that the warming climate has one major drawback: A huge glacial dam holding off oceans of water is about to break, threatening the entire valley. The only chance of survival lies at the other end of the valley. So our three heroes, along with Ellie, Crash and Eddie, form the most unlikely family--in any "Age"-- as they embark on a mission across an ever-changing, increasingly dangerous landscape towards their salvation.

After the events of "Ice Age: The Meltdown", life begins to change for Manny and his friends: Scrat is still on the hunt to hold onto his beloved acorn, while finding a possible romance in a female sabre-toothed squirrel named Scratte. Manny and Ellie, having since become an item, are expecting a baby, which leaves Manny anxious to ensure that everything is perfect for when his baby arrives. Diego is fed up with being treated like a house-cat and ponders the notion that he is becoming too laid-back. Sid begins to wish for a family of his own, and so steals some dinosaur eggs which leads to Sid ending up in a strange underground world where his herd must rescue him, while dodging dinosaurs and facing danger left and right, and meeting up with a one-eyed weasel known as Buck who hunts dinosaurs intently.

When Scrat accidentally provokes a continental cataclysm with a storm, Manny is separated from Ellie and Peaches on an iceberg with Diego, Sid and Granny but he promises that he will find a way to return home. While crossing the ocean, they are captured by the cruel pirate Captain Gutt and his crew. However they escape and Manny plots a plan to steal Captain Gutt's ship and return to his homeland in a dangerous voyage through the sea. But the cruel pirates seek revenge against Manny and his family and friends.

Manny, Diego, and Sid join up with Buck to fend off a meteor strike that would destroy the world.