The film opens with a retro television broadcast summarizing how Reed, Sue, Johnny, and Ben gained their powers during a space mission four years prior. In the present, Reed and Sue discover Sue is pregnant with their first child.
Shalla-Bal, the Silver Surfer, arrives on Earth-828 warning that Galactus is approaching to consume the world. The team travels into space aboard The Excelsior to negotiate. Upon meeting Galactus, the entity scans Sue's womb and detects that her unborn child, Franklin, possesses vast cosmic life energy. Galactus offers a deal: he will spare Earth if Reed and Sue surrender Franklin, whose energy can cure his eternal hunger.
Refusing the horrific demand, the team flees. Mid-flight, while evading Shalla-Bal, Sue goes into labor and gives birth to Franklin. Returning to Earth, the Fantastic Four hold a press conference revealing that they refused Galactus' offer. Terrified citizens turn hostile, attacking the Baxter Building and labeling the heroes selfish.
To save Earth without sacrificing Franklin, Reed constructs quantum teleportation towers across New York designed to displace Galactus into a distant pocket dimension. When Galactus arrives, a fierce battle ensues. Galactus sees through the initial trap, but Sue uses her maximum forcefield power alongside Johnny and Ben to forcefully push Galactus into the portal's boundary, sending the entity away. Earth is saved, but the energy release causes structural fractures across Earth-828's reality.
In the mid-credits scene set four years later, a young Franklin is playing in the Baxter Building. Sue turns away briefly, and when she turns back, Doctor Doom (Robert Downey Jr.) is standing silently next to her son, directly setting up Avengers: Doomsday.