Scrats ständiga jakt på det svårfångade ekollonet skjuter ut honom i rymden där han av misstag sätter igång flera kosmiska händelser som förändrar och hotar ICE AGE-världen. För att rädda sig själva måste Sid, Manny, Diego och resten av gänget lämna sina hem och ge sig ut på en resa som blir full av skratt, äventyr, exotiska platser och på vägen stöter de på en hel drös nya figurer.

Louis, a terminally ill writer, returns home after a long absence to tell his family that he is dying.

Jack Cooper could be a world-class baseball pitcher if he didn't keep buckling under the pressure. He tries to keep his spirits up after he's traded to a minor league team but loses all hope when he discovers that Ed, one of his teammates, is a chimp. Ed used to be the team mascot, but was promoted to third base when the owners realized he had a talent for baseball. As Jack struggles to get used to his new surroundings, Ed helps him regain his confidence on and off the field.