Mamut Manny, lenivec Sid in sabljasti tiger Diego se znajdejo pred novo pustolovščino. Ker se ledena doba počasi bliža koncu, se led pod njihovimi nogami in povsod okrog njih nezadržno topi. To med drugim pomeni, da bo velikanski ledeni jez, ki zadržuje ogromne količine oceanske vode, slej ko prej popustil. Zato bo dolino, v kateri živijo, kmalu zalila voda. Mannyju, Sidu in Diegu ne preostane drugega, kot da na nevarnost opozorijo tudi druge živali in se čim prej rešijo pred neizbežno nevarnostjo. Manny pri tem spozna Ellie, edino samico mamuta na svetu.
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.