Ellie (Queen Latifah) and Manny (Ray Romano) are expecting their first child, and Manny is obsessed with making life perfect and safe for the family, since his first experiences as a husband and father went bad when his family was killed by hunters. At the same time, Diego (Denis Leary) finds himself unable to catch a cocky gazelle (Bill Hader) he has been stalking and decides to leave the herd, believing that he is losing his predatory nature as a tiger. Sid (John Leguizamo) grows jealous of Manny and Ellie and “adopts” three apparently abandoned eggs that he finds in an icy underground cavern and call them Eggbert, Shelly, and Yoko. Manny tells him to put them back, but Sid instead looks after the eggs, which hatch into baby Tyrannosaurus the next morning.

Although Sid tries his best to raise the three dinosaurs, their rambunctious behavior scares away all the other animals’ young and ruins a playground Manny built for Ellie’s baby. A female Tyrannosaurus, Momma, whose eggs Sid stole, soon returns and carries both Sid and her young underground, with Diego in pursuit. Manny, Ellie, Crash, and Eddie (Seann William Scott, Josh Peck) follow as well and discover that the icy cavern leads to a vast jungle populated by dinosaurs thought to be extinct. Here, an Ankylosaurus threatens the herd despite Diego’s efforts to fend it off; they are saved from a further crowd of angry reptiles by an insane, one-eyed weasel named Buckminster, or Buck (Simon Pegg).

Buck has been living in this jungle for some time and is chasing Rudy (a huge albino Baryonyx), intending to avenge the eye he lost to it. He agrees to lead the herd through the jungle’s perils to Lava Falls, where Momma has taken Sid and her babies. In the meantime, Sid and Momma try to outdo each other in feeding the offspring; he loses this contest, but is soon welcomed into the family regardless. The next day, however, Sid is separated from the family and attacked by Rudy. Sid is knocked onto a loose rock slab that is floating on a river of lava and about to plummet over the falls.

As the herd moves toward Lava Falls, Ellie goes into labor and a Guanlong pack strikes, causing a rock slide that separates her from Manny and Diego. Manny doubles back to protect her and Diego fends off further attacks, while Buck takes Crash and Eddie ahead to rescue Sid. Just as he goes over the falls, the trio swoops in on a commandeered Pteranodon only to been chased by a flock of Quetzalcoatlus on the way and saves his life. Manny reaches Ellie, and there is suddenly a reaction, the cry of a newborn baby, then he sees that it is a girl. He wants to name her Ellie, or Little Ellie, but Ellie instead names her Peaches after the fruit (and the codeword they had chosen for Ellie to use if she went into labor during the trip). Sid is saddened at the fact that he never had a chance to say goodbye to "his" children as he returns to the herd and learns of Peaches' birth.

Before they can exit the jungle, Rudy attacks at full force; Buck lures Rudy away from the group and is nearly eaten himself, before Diego saves him at the last second. They then ensnare him briefly, but he escapes and resumes his onslaught. The herd is saved by the timely arrival of Momma, who charges at Rudy and knocks him off a cliff before roaring her victory. As she and her children wish Sid well, Buck – now without a purpose in life since Rudy is gone – decides to join the herd and live on the surface. However, a distant roar tells him that Rudy is still alive; he changes his mind and sends the herd home, blocking off the path to the underground jungle at the same time so that no one else can go down there. Manny and Ellie welcome Peaches into their frozen world and admit that Sid did a good job looking after Momma's children (though Manny tells Diego that he will never let Sid babysit Peaches). Diego decides to remain with the herd, while Buck stays where he wants to be: underground, battling it out with Rudy.