The movie opens out in space as a strange alien planet slowly fades away and implodes. A mysterious blue entity leaves the planet prior to its destruction, and is next seen flying through the atmosphere over Earth. At the same time, a number of strange circumstances unfold (the China Sea freezes over and the Sphinx is covered with snow).
A news reporter states that the FAA was forced to ground all flights as a result of these events. Reed Richards (Ioan Gruffud) watches the news from the airport and is disgusted because the news is more focused on his upcoming wedding to Sue Storm (Jessica Alba) than the strange events.
The Fantastic Four board the plane now cleared for flight. Ben Grimm (Michael Chiklis) is obviously uncomfortable crammed into a Coach seat. Johnny Storm (Chris Evans) suggests that the team get an endorsement and form their own private airline. He then leaves to fly himself back home as the Human Torch.
Back at the Baxter Building (the team's headquarters), Sue and Reed discuss the details for their upcoming wedding. Johnny shows off his prototype new uniforms to the team (they are loaded with company logos and product placement). Johnny tries to snoop on Reed's latest product while Reed explains that the global disturbances are being caused by a similar tyoeof cosmic radiation that originally gave the Fantastic Four their powers.
Johnny insists on throwing Reed a bachelor party. Reed is opposed to the idea, until Johnny blackmails him with the threat of telling Sue that Reed is spending more time researching disturbances than taking care of his end of the planning.
The mysterious entity passes over the nation of Latveria, and its residual energy frees Dr. Victor Von Doom (Julain McMahon) from his imprisonment.
Johnny takes Reed and Ben to a nightclub for Reed's bachelor party. Reed and Ben are obviously uncomfortable (Reed because of his shyness, Ben because of his Thing powers).
A military force led by General Hagar (Andre Braugher) arrives at the Baxter Building to see Reed. Sue takes them to the club where they see Reed dancing (making full use of his Mr. Fantastic abilities) and Reed is embarassed.
Ben explains to Sue the history Reed has with General Hagar: Hagar had designed a new defense system several years ago, while Reed testified that the technology it called for was unreliable. General Hagar is concerned about the anomolies occurring worldwide, and shows the team sattelite photos of the mysterious entity. The generals' assistant, Captain Frankie Raye shows the team photos of craters that have been appearing in the same spots as the entities appearance. Hagar asks for a way to track the mysterious entity, but Reed turns him down because his wedding is in a few days. Johnny flirts with Captain Raye as they leave, but she shoots him down.
Later on, Ben finds out that Reed has decided to build the tracking system for the general anyway. Ben (and Johnny, who flies in when Reed is building) both agree to keep quiet.
The next day is the date of Sue and Reed's wedding! Hundreds of guests file in (including a cameo by Fantastic Four creator Stan Lee).
Sue discusses her future with Alicia Masters (Kerry Washington), Ben's blind girlfriend. Susan realizes that she has a zit on her forehead, but is able to conceal it with her Invisible Woman abilities.
Reed finishes the satellite tracking system less than an hour before the wedding begins. He is happy to have finished the project, but once Ben points out that he is about to be married, Reed goes limp with shock.
Johnny comes in and has a brief discussion with Ben about his relationship with Alicia, at which point Ben almost breaks Johnny's skull out of anger and embaressment.
Victor Von Doom begins to track the mysterious entity, trying to figure out the power that brought him back to life.
As Reed & Sue stand before the minister, Reed's Palm Pilot goes off telling him that the sattelite tracker has come online. Sue is outraged that he lied to her. The entity then passes through New York City, causing a massive power outage and sending one of the news choppers covering the wedding flying towards the rooftop.
Sue uses her force field ability to block the chopper from hitting the guests. Ben jumps in and rips off the tail of the helicopter to prevent anyone from getting cut to pieces by the blades. As the entity passes overhead, Johnny shouts "Flame ON!" and gives chase.
The Human Torch follows the mysterious thing through the city and watches it pass through a building- thus getting his first look at The Silver Surfer (Doug Jones). Torch and Surfer begin an Ariel chase across half the country, but the Surfer ends it by grabbing Johnny by the throat and levitating him to the stratosphere, then sending Johnny flying back down to earth. Johnny is barely able to re-ignite his flame in time to stop crashing.
In space, the Silver Surfer contacts his master and awaits further orders.
Johnny describes the Silver Surfer to the team, who are skeptical at first. General Hagar orders Reed to find another way to track the Surfer.
Sue confronts Reed, worried that the two of them can never have a normal life if they continue to act as part-time superheroes. Sue is unsure if they can ever actually raise a family together.
Johnny, still dazed from his encounter with the Surfer, tries to fly but ends up falling off the building. Sue runs outside to check on him but when she touches his forehead Sue suddenly bursts into flames! Johnny shouts "Flame ON" but he only succeeds in turning invisible. Reed sees what has happened and runs outside. He suggests that Sue touch Johnny again, and they revert to their normal powers- though Sue is now naked after burning off her clothes.
Reed does a physical on them both and sees that Johnny's molecules are in a state of flux, and that he may switch powers with any of them just by touch. Ben immediately takes advantage of this and grabs Johnny's shoulder, turning him into the Thing! Johnny is appalled by his new appearance and grabs Ben, changing them both back.
Sue is still watching the news when she is joined by Reed. Reed announces that he has decided to give up being a hero once they are married. She is ecstatic, but Johnny overhears them and is angered.
Victor Von Doom calculates the next appearance of the Silver Surfer. He confronts the cosmic entity, suggesting a partnership between the two of them. The Surfer ignores Doom's idea and blasts him with a burst of cosmic energy. Doom is angry, but then notices that the energy is restoring his normal organic appearance.
Johnny tells Ben about Reed & Sue's plan to leave. Ben is mad but decides that something like this is something that they can't argue with.
Reed points out that the Silver Surfer's energy has been tracked to several other planets, which are now lifeless husks. They realize that 8 days after the Surfer's appearance on any world, that planet dies. Reed gets the idea to track the Surfer using the coordinates of the craters he leaves behind.
En route the the newest spot (in London), Johnny confronts Reed & Sue about their decision and they argue.
The Surfer's passing through causes The London Eye (London's famous Ferris wheel) to be damaged, and many civilians are in danger. The Fantastic Four quickly rush to save them, with Johnny trying to chase the Surfer again. But Johnny accidentally collides with Reed and they switch powers. Ben & Sue almost let the Ferris wheel collapse before Reed gets the idea to use Human Torch's power to weld it back into place. Reed sets back down and quickly reclaims his rightful power from Johnny, angry that Johnny's recklessness almost killed a lot of people-including Sue.
General Hagar is outraged at the Fantastic Four's failure. He has decided to get extra help: Victor Von Doom. Ben, outraged that their old foe is still alive, attacks. Reed convinces Ben to back off, and asks what Victor has to contribute.
Victor shows a recording of his previous encounter with the Silver Surfer. They observe that the Surfer's energy attack originated from his board, and theorize that if they can divide him from the board the Surfer will be vulnerable.
Johnny and Ben spend the night at a bar, discussing the turn of events. Johnny asks Ben what he wants to do if the world is indeed coming to an end. Ben admits that part of him would want to go down fighting, but he mostly would want to spend his last moments with Alicia. Johnny agrees, apparently jealous that Ben has someone so special to him.
Reed has surrounded himself with databases, working around the clock to find the solution without Victor's help. Sue comes in and reassures him, ordering Reed to relax. Sue mentions that Reed's pulse must be overexerted, and the word "pulse" inspires Reed: he can create an energy pulse generated by a power field to divide the Surfer from his board. Reed requests some equipment from General Hagar to build the power field.
Sue confronts Victor about his intentions and his return. Meanwhile, Johnny flirts with Frankie again but she blows him off as a reckless jokester.
The Fantastic Four arrive at the newest coordinates and begin to set up the pulse generators. Ben has a humorous confrontation with a bear when setting up his section of the generator.
Susan is setting up her generator when the Silver Surfer appears in front of her. Sue approaches the Surfer, asking him why he is working to destroy the planet. The Surfer claims that he has no choice; that he is not the destroyer but merely a beacon.
General Harding spots the Surfer and opens fire. Silver Surfer merely swats down the missiles with his cosmic powers. Reed activates the pulse system, knocking the Surfer off his board (and in the process turning his body from bright silver to a dull, tarnished gray).
General Harding brings the Surfer and the board to a hideout in Siberia for further study. He places the Fantastic Four under "house arrest" until they are finished studying. Sue decides to go out and confront the Surfer. She asks him who the real destroyer is, and the Surfer responds (showing her an image) that the true destroyer is his master, a vast cosmic entity known by many names and forms which his people refer to as Galactus. The Silver Surfer explains that his service spares his homeworld from the destroyer. Surfer explains that he is compassionate towards Sue because she reminds him of his beloved.
Out in space, a vast cloud is shown moving towards Earth. The destroyer is drawing closer.
Victor is permitted to do tests on the board. He uses a special device to free the board from its confinement and bond with it. General Hager tries to stop him, but Doom blasts him with his new cosmic energy and vaporises the general.
The Fantastic Four escape from confinement, also freeing the Silver Surfer. Frankie is reluctant to let them leave, but Johnny pleads with her and he manages to convince her.
As they get outside, Reed summons his new invention- the FantastiCar, a flying hovercraft for the team. Reed, Sue, Ben and the Surfer climb in (Johnny flies along beside them). The Silver Surfer confesses his real name- Norrin Radd. He agrees to try and help them.
The Fantastic Four track Victor to Southeast China, and attack. They are able to lure him over the land, but must abandon the FantastiCar after he attacks it. Norrin confronts Doom, who fashions a javelin from the board's energy and hurls it at him. Sue steps in front of Norrin, conjuring up a force field to protect them both, but the javelin passes right through the force field and impales Sue, mortally wounding her. Seeing no other option, Johnny suggests that all of the other team members transfer their powers to him. They argue, but Norrin points out that they have no other choice- Galactus has arrived, and is extending its tendrils into the planet to devour it.
Reed tells Johnny to aim for the remote emitter Doom is using to connect himself to the board. Ben, remembering his thought of going down fighting, takes control of a giant crane and uses it to attack Doom. The combined efforts of the team's powers is successful and Doom crashes into the ocean, sinking out of sight.
Norrin re-connects with his board, and infuses Sue with a small part of his cosmic energy, restoring her to life. The Silver Surfer tells Reed to treasure every moment with Sue, and flies off to face the cosmic entity. He is joined midway by Johnny, who uses the last of his combined powers to give the Silver Surfer a boost into the cosmic storm.
In the heart of the cloud, Silver Surfer tells Galactus that he will no longer be a servent. Norrin Radd charges up a massive amount of cosmic energy and then releases a huge blast, stopping the cosmic entity by apparently destroying them both.
The Fantastic Four, including the revived Sue, are thrilled to see that the destruction of the planet has stopped but saddened by the loss of the Surfer. Johnny accidentally comes into contact with Ben, but is shocked to see that nothing happened. To everyone's relief, Johnny's second encounter with the Surfer has restored his powers to normal.
Sue reveals that she has decided against her past ideas and does not want to break up the team, since they just saved the world together. Reed agrees that they cannot run away from their responsibilities and that people do not have to be "Normal" to have a family. Reed also has an idea regarding the prospect of a wedding.
Sue and Reed decide to hold a Shinto-style wedding while they are still in China. They must rush through the ceremony when Reed's pager alerts them of new danger. Sue tosses the bouquet to the women in the audience (including Frankie, who apparently has decided to pursue a relationship with Johnny). When it looks as if Frankie might catch the bouquet, Johnny "accidentally" sneezes and burns up the flowers.
The Fantastic Four boards their newly restored Fantasticar and speeds off to another adventure!!!
In a bonus scene partway through the credits, the Surfer and his board are seen floating through space. The Surfer appears to be dead after his encounter with Galactus. But suddenly the Surfer's board turns and begins to move toward him.