- Jon Hamm as Mr. Fantastic
- Joel Edgerton as The Thing
- Kelsey Grammer as Mole Man
- Lynn Collins as Invisible Woman
- Alex Pettyfer as Human Torch
- Jude Law as Victor von Doom
- Dee Bradley Baker voices Dragon Man
Reed Richards is a scientist whose best friend, Ben Grimm, is a pilot. Reed dreams of getting his own ship in to space in order to study Venus, and Ben offers to pilot it. With funding from Reed's old college rival, Victor von Doom, Reed and Ben get their ship in the air, and take Reed's girlfriend, Sue Storm, and Sue's brother, Johnny, with them. In space a meteor hits the ship while it was on auto pilot. The cosmic radiation from the meteor gives the four fantastic powers
- Reed gains the ability to stretch his body.
- Sue gains the ability to turn invisible.
- Johnny gains the ability to turn his body into flames.
- Ben's skin turns into an orange, rock-like substance giving him super-strength.
When the ship crashes, some of the meteor radiation leaks through the ground and into the soil which is proving fatal to the secret underground race known as the Subterraneans. When Victor's next project (a tunneling probe which will travel to Earth's core in order to study it) opens a gateway for the Subterraneans to reach the surface, the leader of the Subterraneans, Mole Man, swears revenge against the people who posioned his race. Reed and the gang decide to use their powers to become heroes, and stop Mole Man before he creates an all-out war.