A creature named Annihlus appears in Reed's lab, soon followed by his mortal enemy, Blaastar. The Fantastic Four learn these two enemies come from the Negative Zone and must return them before it's too late.
The Fantastic Four are at a charity function at Rockefeller Center, when the building is dragged underground. It's discovered that the Mole Man is responsible and he plans for world domination.
Reed, Johnny, and Ben arrive in ancient Greece, with only forty-eight hours to find the casket. Their problems multiply, however, when they get into the middle of the Battle of Thermopalye.
Sue learns about Doctor Doom's past, while the others deal with the castle's traps. When they find him, Doom offers a deal: travel back in time to retrieve an ancient casket or Sue will be killed.
The Skrulls let loose a new danger for the Fantastic Four to face, a being that possesses their combined powers: Super Skrull! Will the team be able to take this villain down?
As Galactus' plans unfold, the Fantastic Four try to reason with him, but it proves futile. The only way to defeat Galactus now, puts Johnny's life in mortal danger. Meanwhile, the Silver Surfer sees Alicia and his loyalties begin to change.
The enigmatic Watcher warns the Fantastic Four of the impending arrival of the herald of Galactus, the Silver Surfer. They learn if he summons his master, all of Earth will be devoured.
The Skrulls, a race of green skinned shape shifters, come to Earth and impersonate the Fantastic Four. They attempt to discredit them, hoping to keep them from interfering in their plans to conquer Earth.
The Puppet Master turns the Thing against Fantastic Four, but his plans fall apart when his step-daughter, Alicia, falls in love with the Thing and sides with the team.