In the next chapter of the prehistoric saga, Scrat, the hapless saber-toothed squirrel, once again sets off a cataclysmic chain reaction. His eternal pursuit of the elusive acorn catapults him into outer space, where he inadvertently sets off a series of cosmic events that threaten the Ice Age world. Back on Earth, the impending disaster prompts Manny the mammoth, Sid the sloth, and Diego the saber-toothed tiger to leave their home. This looming threat of a meteor shower has the potential to wipe out all life, leading the herd to seek a solution to save themselves and their friends.

As the familiar characters embark on their quest, their path is filled with challenges and an assortment of new characters. Among them is Buck, a one-eyed weasel and dinosaur hunter who serves as the guide on their tumultuous journey. Alongside the impending celestial peril, personal stories unfold: Manny grapples with the upcoming marriage of his daughter Peaches and his difficulty with letting go, while Sid longs for romantic companionship, and Diego and his partner, Shira, consider if the world they live in is too dangerous to raise a family. Together, the group must traverse a landscape replete with both beauty and danger, confronting new environments and creatures, in a bid to survive the global "scrat-tastrophe.