At Culver University in Virginia, Bruce Banner, a scientist and radiation expert, meets up with his girlfriend’s (Betty) father General Thaddeus ‘Thunderbolt’ Ross to replicate a World War II bio-enhancement formula.
The replication process of recreating the World War II “Super Soldier” experiment fails and Bruce is exposed to Gamma radiation. This exposure causes Bruce to transform into the Hulk for brief periods of time whenever his heart rate rises above 200. The Hulk eventually injures and kills most people at the lab causing Bruce to become a fugitive on the run from the U.S. government and General Ross who wants to weaponize the Hulk procedure.
Bruce continues this search for a cure to his condition while working at a bottling company five years later in Rocinha, Rio de Janeiro in Brazil. He collaborates with a mystery colleague who he knows as Mr. Blue on trying to find a cure for his condition. He also takes yoga classes which has helped him keep his Hulk persona under control as he has not transformed for 158 days.
Bruce’s cover is soon blown when he accidentally cuts himself and a drop of his blood falls into a bottled drink and is consumed by an elderly man causing him to have Gamma sickness. General Ross uses the bottle to track Bruce and dispatches a special ops squad led by Russian-born British Royal Marine Emil Blonsky.
Bruce is able to adequately defend himself from Blonsky’s team as the Hulk; however, when General tells Blonsky about how Bruce became the Hulk, Blonsky decides to get injected with the Hulk serum. The serum makes Blonsky agile and incredibly fast and strong, but costly side effects begin to kick in as he begins to demonstrate impaired judgement and skeletal deformity.
Back at Culver University, where the Hulk was formed, Bruce meets up with Betty who is now dating a psychiatrist, Leonard Samson. On the day he decides to leave, he is attacked by General Ross and Blonsky’s forces, who are tipped off by Samson who grows suspicious of Bruce. This causes a fight to breakout outside the University and Bruce transforms in the Hulk once again.
General Ross’s forces are defeated by the Hulk but Blonsky’s clouded judgement causes him to try to take on the Hulk on his own. Blonsky used his speed, strength, and agility to taunt and annoy the Hulk who then seemingly kills off Blonsky.
The Hulk escapes with Betty, and when he reverts back to Bruce, the duo go on the run. Bruce makes contact with Mr. Blue again, who claims that he has a possible cure to Bruce’s condition and asks Bruce to meet up with him in New York. Mr. Blue is revealed to be cellular biologist Dr. Samuel Sterns.
After a successful test, Dr. Sterns reveals to Bruce that the antidote could only reverse each of his transformations. Dr. Sterns tells Bruce that he has replicated Bruce’s blood samples into a large quantity, explaining how he intends to use it to explore its huge potentials to medicine.
However, Bruce fears that his blood samples could fall into the hands of the military who would decide to weaponize it, so has intentions to destroy the samples. Meanwhile, Blonsky is revealed to have survived and he reunites with General Ross’s forces to try to capture the Hulk one more time.
They are successful as the capture Bruce and Betty, carting them away in a helicopter while Blonsky who has always been jealous of the Hulk’s abilities orders Stern to inject him with the Hulk’s blood, despite Stern’s strong warnings that the combination of the super soldier serum and the Hulk serum could turn him into an “abomination.”
Blonsky still goes ahead with it; unfortunately the experiment drives him insane and causes him to transform into a monster that is two times the size and strength of the hulk. Bruce eventually comes to terms with the fact the he is the only one that can face Abomination, who has begun to destroy the city.
After much persuasion, General Ross releases Bruce who leaps from the helicopter, transforming into the Hulk before he lands. A massive fight ensues, but the Hulk defeats Abomination. The Hulk is briefly reunited with Betty for a moment before he flees from New York.
One month after, Bruce is able successfully pull off a controlled transformation into the Hulk in Bella Coola, British Columbia. A final scene eventually shows Tony Stark walk up to General Ross in a bar to tell him about a team he is putting together.