Bruce Banner (Edward Norton) was a scientist turned fugitive when he was affected by doses of gamma radiation and transformed into the beast within him---The Incredible Hulk. (Fred Tatasciore)
Somewhere in a town in South America, Bruce is chased by soldiers led by Emil Blonsky (Tim Roth), who were sent by General Thunderbolt Ross (William Hurt). Cornered inside a factory, Banner transforms into the Hulk, defeats the soldiers, and flees the country. After arriving in New York City, the Hulk saves the life of Rick Jones, a teenager who had been captured by soldiers working for an organization called the Enclave. It is the brainchild of four scientists, each with his own private army, and use Manhattan as a giant test site. Hulk saves him from Minerva Sector's soldiers who were using a mind control device on him. Soon after, the Hulk further protects Rick Jones from Enclave's Ceres and Jupiter Sectors, and the two become friends.
Soon after, Banner begins to work with Dr. Samuel Sterns (Tim Blake Nelson), who had been his contact in South America. Banner goes to talk to Simon Utrecht, a ruthless businessman whose research is similar to his own and is planning to test radiation on himself and three other participants. The Hulk fights off the Army coming to arrest him but is then confronted by the U-Foes, a superhuman group consisting of a metallic being called Ironclad, a telekinetic being named Vector, a humanoid cloud named Vapor, and an inside-out, radioactive being called X-Ray. The Hulk manages to beat them, though the U-Foes vow revenge. Under Sterns' direction, Hulk retrieves special nanites for Sterns to use in his research.
Major Glenn Talbot then dispatches the Army to take down Hulk with total disregard for civilian casualties. Hulk fends off an army attack under his direction, then destroys their computer targeting systems and defeats Blonsky again. Hulk then stops the Enclave's Minerva Sector from siphoning energy from the city, then foils Ceres Sector's chemical weapon attack. After an attack on a military base, during which Talbot's forces fire on the press as well as the Hulk, Talbot goes into hiding. After attacking another base, Hulk learns that Talbot has captured Rick. Hulk rescues Rick, and Talbot goes on the run.
After escaping Talbot's soldiers, Rick tells Bruce that Enclave is creating a massive mind-control device and needs the data to create a countermeasure. Working together, Hulk and Rick manage to destroy the device. Enraged, the leaders of Enclave unleash the robotic monster Bi-Beast against Hulk. Hulk engages Bi-Beast in battle and destroys it, causing Jupiter Leader to take charge after Ceres and Minerva's failures. Hulk subsequently takes down Jupiter Sector's earthquake generators, Vulcan Sector's laser turrets, and the control dish for an orbital laser cannon. Bruce is then contacted by Sterns that they can try to cure him, if they can obtain three items to build a Gamma Charger to elevate his gamma levels for the cure. Hulk successfully retrieves all three of the items.
Banner then heads to the university where his old research data is only for Betty Ross (Liv Tyler) to get the data before all of it is deleted by her father. When General Ross' soldiers grab Betty, Bruce turns into the Hulk and attacks the army's deployment points. Hulk then ends up in an third fight with Blonsky, who has received treatment that enhances his physical capabilities. Hulk manages to defeat him and makes off with Betty.
Betty then tells Bruce that her father is going to attack an Enclave base, clearly underestimating their power. At her request, Hulk takes down the base before the Army arrives. Hulk then prevents the Enclave soldiers them from stealing the Army's Hulkbuster technology built by Stark Industries, leaving the armor pilots wondering if General Ross has him figured wrong. Afterwards, Hulk then helps the Hulkbusters destroy the Enclave F-POD weapon. After Vulcan Leader's failure, the Enclave leaders conclude that they must either kill the Hulk themselves or let the Army do it for them.
Sterns then tells Hulk that they can test their device if Hulk can obtain a genetic simulator from Enclave. Hulk uses the device to disable an Enclave bio-weapon, causing Sterns to conclude that the cure works. Hulk then has to guard a truck containing an experimental weapon that General Ross is having transported. When Talbot steals the weapon, Hulk retrieves it and gives it to Rick so he can destroy it. When Talbot kidnaps Betty, Hulk fights a Hulkbuster to destroy the generators trapping her in a cage. Once the Hulkbuster sees who he has kidnapped, he orders his troops to fall back. General Ross sends his troops to arrest Talbot, who is now wearing a special nuclear-powered Hulkbuster. Hulk joins the fight and defeats Talbot, throwing him into the air where he explodes.
Despite everything Banner has done to help, General Ross still captures Banner and takes him and Betty away. Afterwards, Blonsky forces Sterns to inject him with Banner's gamma-irradiated blood, transforming him into the monstrous Abomination, who then rampages through the city. Seeing as he's the only one who can stop him, Banner jumps from the helicopter and transforms into the Hulk. After a lengthy battle, Hulk defeats the Abomination and flees the city. Betty tells her father that she hopes it was worth it.
