The film introduces us to two unlikely best friends named Reed Richards and Ben Grimm, they're both attending the same university. Ben attends there due to a football scholarship and Reed attending due to a scholarship as well. In their spare time, they both work at a convenience store to pay off their loans, as they're only partial. But after, Ben is the one to attend parties and socialize while Reed stays up in the dorm to study. One day, Reed gets a special speaker for one of the classes he takes. The visitor's name is Franklin Storm. Franklin is looking for volunteers for an expedition to a viewing of a scientific breakthrough: The birth of an alternate universe, many people turn in their applications. But the two finalists end up being Reed and another student named Victor Domashev who, in his spare time, is a blogger. They share similar interests but Victor has a certain arrogance and pride but it's covered by his charisma. Ben gets jealous somewhat by the newfound friendship between Reed and Victor, but Reed quickly dismisses this.
It's revealed that Reed, between the two, has earned the chance to explore the alternate universe along with Dr. Storm. Victor becomes enraged and, due to Reed's conscience, tries to ask Victor to come along, he declines and drops out and goes back to Latveria to pursue his own dream. Reed then apologizes to Ben about the way he has acted and asks if he wants to come watch the event. The two other candidates they meet for the expedition is Storm's own son, Johnny, and his adopted daughter Sue. Johnny parties frequently, and while Sue is somewhat the same, she is looking for a career in acting. Reed unintentionally insults her about her career and she ends up hating him for quite a while. Johnny and Ben get along pretty well. On the day of the expedition, Reed tinkers with the machine for a moment and stands aside, the machine is a teleporter, and gains the nickname " the N-Zone." Reed, Ben, Sue, Johnny, and Franklin marvel at the design, however the machine malfunctions due to the last minute set-up. It ends up teleporting the four and irriadiating them with cosmic energy. Luckily, all four survive but end up in hospital beds. The government then finds out about Dr. Storm's failure and have him arrested, Victor finds out about this and builds his own N-Zone, the aftermath leaves Domashev horribly disfigured and burnt, he vows himself to bring an end to Franklin Storm and builds a costume to conceal his burns. The group of four wake up in the Baxter Building nursing room, being monitored by the military.
The group are angered and try to break free, they are consulted by a member of the US government, stating that they will be running tests to ensure that they are safe from any radiation from unknown entities. Weeks pass and eventually there is no sign of anything wrong with them. Reed being curious, decides to run tests, while Ben and Sue try to ignore like nothing has happened. Johnny is playing Fifa '15 and when his team loses, he gets angry and spontaneously catches on fire. Reed checks to see what's happened and Johnny is revealed to have his body combusted in flames. Reed checks to see if he has the same powers, but instead it shows him being able to stretch his entire body into a spectacular length. Sue is angered by the government's actions and Ben tries to calm her down, Sue suddenly gets infuriated and blasts a psionic energy around the entire neighborhood. Ben gets blasted by her and is thrown to the side of a trailer, he's knocked unconcious. Sue brings him back to the Baxter Building, stating that she blasted an energy of a sort. Johnny and Reed show off their powers to Sue and the trio try to find out the explanation of their differing powers. Meanwhile, Ben suffers a violent transformation into a rock-hard creature, the trio investigate his room to find him fully transformed, Ben looks into the mirror, throwing a fit, before dropping down and crying. This pushes Reed into a work-a-holic type attitude, secluding himself.
Sue and Johnny comfort Ben, trying to find different ways to approach his newfound life. Johnny reconstructs the gym in the building so it becomes a fighting center for Ben, while Sue checks on Reed. Reed apologizes to her, Sue accepts, they share a tender kiss. Dr. Storm is released from a holding cell and the government brings him back to the building. They are attacked by Domashev, now calling himself Dr Doom, he attacks the van, killing all the soldiers, Storm escapes barely, Doom throws a tracer onto him. Franklin returns to see the team playing around with their abilities, Storm, astonished and horrified by the sight, decides to train the team to harness their abilities. Storm talks to Ben and says that him and Reed will find a cure for him. Reed consults Franklin about the differing powers and Ben's state, Franklin gives a conclusion that the power they receive are reflective of their personality. Reed expands his mind to greater knowledge, Johnny is a hothead, Sue, despite being popular, was always outcasted by her "friends", and Ben having a sensitive personality hides it with his rock-hard attitude.
Doom finds out that the group has powers of their own and is furious, he builds a series of robots and makes a fleet to attack New York City, he himself builds jet propulsors to enable himself to fly. The bots are seen attacking in daylight, he orders them to do any means necessary to find Storm and his team, he hacks into the broadcasts of NY to demonstrate his power to the city. The four see this on the news and tell Franklin they have the powers to defeat him. Franklin agrees and gives them containment suits to fight the army off, it's made of a durable lightweight lycra, covering all the body, obtaining also a helmet that can flip on/off. They go and fight the battle,suceeding, but soon find out that Victor is the source of this chaos. Victor goes up to the building and finds Storm to attack him, he is beaten to death before the team arrives to find him. Sue and Johnny mourn his loss before Johnny heads out in rage to look for Doom. Reed comforts Sue as Ben is trying to contact Johnny. Doom is shown to be in the building but accessing the N-Zone. Sue, Ben, and Reed construct a plan to defeat him, there, they attack him while the portal is loading. It's not enough, but Johnny comes in to fight alongside, Doom's wardrobe is charred and it burns him more, engraving the metal with his body, the portal opens and Doom beats the four, before entering the N-Zone, his body is not able to withstand the radiation, Reed offers to help him out, but Doom declines, striking Reed and closing the portal.
A private funeral is held for Franklin before the team is taken into custody by the government, there is a public hearing regarding their acts on New York. Reed speaks for the group and essentially becomes the leader, the government decides not to hold them for the destruction, but instead hold Franklin Storm responsible. The four friends rebuild the Baxter Building, with Reed continuing to run tests, Sue starts making new costumes, stating the suits are a bit clunky. Johnny comes up with codenames, and Ben is seen coming to terms with his new self. The four members hug each other but are interrupted by a small earthquake outside. A giant green monster grows from the ground and starts destroying the city. The four go outside to confront the monster, and find that it's controlled by the Mole Man. The Mole Man asks who they think they are, and Johnny delivers a response: The Fantastic Four.