At Culver University in Virginia, Gen. Thunderbolt Ross meets with Dr. Bruce Banner (Edward Norton), who is not only his colleague but also the lover of his daughter Betty (Liv Tyler). Ross discusses an experiment intended to render humans immune to gamma radiation, which he claims is part of a World War II "super soldier" program he aims to replicate. However, the experiment fails and results in Banner being exposed to excessive gamma radiation, leading to his transformation into the Hulk during moments of extreme emotional distress—specifically, whenever his heart rate exceeds 200 bpm. This incident wreaks havoc in the lab, resulting in injuries and fatalities. Consequently, Banner becomes a fugitive, pursued relentlessly by Ross, who harbors ambitions of weaponizing the Hulk's abilities.
Five years later, the narrative shifts to Rio de Janeiro, Brazil, where Banner has managed to find work at a bottling factory while diligently searching for a cure. During this time, he communicates via the Internet with a mysterious colleague known as “Mr. Blue,” and adopts the moniker "Mr. Green." To maintain control and avoid transformations, he is practicing meditative breathing techniques and celebrates 158 days without incident. However, an unexpected turn of events occurs when a drop of his blood accidentally contaminates a beverage that an unsuspecting elderly man in Milwaukee consumes, leading to catastrophic medical consequences.
In response to this discovery, Ross dispatches a SWAT team to apprehend Banner, led by the formidable Emil Blonsky (Tim Roth), a Russian-born British Royal Marine. Following an intense showdown, Banner’s transformation into the Hulk allows him to overpower Blonsky's team. As Ross recounts the events that transformed Banner, Blonsky opts to undergo enhancement through a serum linked to the same super-soldier initiative, which dramatically increases his capabilities but gradually distorts his body and mental state.
Upon returning to the university, Banner encounters Betty again, now involved with psychiatrist Leonard Samson. Subsequently, Ross and Blonsky’s forces, alerted by the observant Samson, ambush Banner, triggering his metamorphosis into the Hulk. An explosive confrontation ensues outside the university, where Ross's efforts falter, forcing a retreat. Undaunted, Blonsky engages the Hulk, resulting in a devastating defeat for him. As the dust settles, Banner, having reverted back from the Hulk, goes on the run with Betty, spending a tense night together in a motel, hindered by his fluctuating heart rate.
Banner soon contacts Mr. Blue, who is revealed to be Dr. Samuel Sterns. He shares news of an experimental antidote that may help Banner, but warns that it could only reverse individual transformations. Sterns has synthesized Banner's blood and harbors ambitions to exploit its "limitless potential" for medical advancements. Alarmed at the prospect of the military utilizing the Hulk's power, Banner beseeches Sterns to destroy the supply. Meanwhile, Blonsky resurfaces, having fully healed from their last encounter, and rallies Ross's troops for another attempt to capture Banner.
This time, they succeed, capturing Banner and Betty aboard Ross’s helicopter. As events unfold, Blonsky coerces Sterns into injecting him with Banner's blood, driven by his thirst for Hulk-like power. Sterns forewarns him that this combination may transform him into an "abomination," but Blonsky's ambition prevails, leading to a monstrous transformation that allows him to overshadow the Hulk in stature and strength, albeit at the cost of his sanity.
Recognizing that only the Hulk can counter this new threat, Banner persuades Ross to release him. He jumps from the helicopter and lands, almost immediately transforming into the Hulk. In an epic confrontation through Harlem, the Hulk ultimately manages to defeat the Abomination, grappling him with a massive chain and almost delivering a fatal blow, but he pauses at Betty's plea for mercy. After their brief moment of tranquility, the Hulk retreats and escapes New York.
A month later, in Bella Coola, British Columbia, Banner embraces his condition rather than suppressing it, attempting to transform deliberately, and revealing a smile as his eyes take on a green hue. In a notable post-credits scene, General Ross is approached by Tony Stark, who unveils the formation of a "team."
