A saber-toothed squirrel (known as Scrat) is trying to find a place to store his prized acorn. Eventually, as he tries to stomp it into the ground, he causes a large crack in the ground that extends for miles and miles and sets off a large avalanche. He barely escapes, but finds himself stepped on by a herd of prehistoric animals. The animals are trying to avoid the ice age by migrating south. Sid, a clumsy ground sloth left behind by his family, decides to move on by himself but is attacked by two Brontops whom he angered. Sid is soon saved by Manfred (“Manny”), an agitated mammoth who fights them off and is heading north. Not wanting to be alone and unprotected, Sid follows Manny. Meanwhile, Soto, the leader of a Smilodon pride, wants revenge on a group of humans by eating the chief’s baby son, Roshan, alive. Soto leads a raid on the human camp, during which Roshan’s mother is separated from the rest and jumps down a waterfall when cornered by Soto’s lieutenant, Diego. For his failure, Diego is sent to find and retrieve the baby.
Later, Sid and Manny spot Roshan and his mother near the lake, having survived her plunge. The mother only has enough strength to entrust her baby to Manny before she disappears into the water. After much persuasion by Sid, they decide to return Roshan, but when they reach the human settlement, they find it deserted. They meet up with Diego, who convinces the pair to let him help by tracking the humans. The four travel on, with Diego secretly leading them to his pack for an ambush.
While having small adventures on their way, they reach a cave with several cave paintings made by humans. There Sid and Diego learn about Manny’s past and his previous interactions with the human hunters, in which his wife and son were killed, leaving Manny a cynical loner. Later, Manny, Sid, Diego and Roshan almost reach Half-Peak but encounter a river of lava. Manny and Sid, along with Roshan, make it safely, but Diego struggles, about to fall into the lava. Manny rescues him, narrowly missing a fall into the lava himself. The herd takes a break for the night, and Roshan takes his first walking steps to Diego.
The next day, the herd approach the ambush, causing Diego to confess to Manny and Sid about the ambush, and he tells them to trust him. The herd battles Soto’s pack, and a short fight ensues. As Soto closes in for the kill on Manny, Diego leaps and stops Soto, who wounds Diego in the process. Manny knocks Soto into a rock wall, causing several sharp icicles to fall on Soto, killing him. The rest of the pack then retreats. The group then mourns for the injury caused to Diego. Soon, Manny and Sid manage to return the baby to his tribe, and Diego rejoins them, as the group begins to head off to warmer climates.
20,000 years later, Scrat, frozen in the ice, ends up on the shores of a tropical island. When the ice slowly melts, the acorn is then washed away. He mistakenly triggers a volcanic eruption, while stomping a coconut into the ground.