Jennifer Walters, the cousin of Bruce Banner (Hulk), is the small and somewhat shy daughter of Los Angeles County Sheriff William Morris Walters. Agents of Nicholas Trask, a crime boss who had crossed paths with her father, shot and seriously wounded her on a day that Bruce Banner happened to be in town for a visit. Since no donors of her blood type were available, Banner provided blood for a transfusion; his radioactive blood transformed Jennifer into the green-skinned She-Hulk when the mobsters tried to finish her off at the hospital.

As She-Hulk, Jennifer possessed powers similar to those of her cousin, though at a reduced level. She also possessed a less monstrous, more amazonian appearance and most notably was never prone to the type of rage induced rampages of her cousin. Initially, the transformation to her She-Hulk form was triggered (as with Bruce Banner's) by anger. She eventually gains control of her transformations when Michael Morbius cures her of a lethal blood disease.

Eventually, Jennifer decides that she is going to retain her She-Hulk form permanently - preferring the freedom, confidence, and assertiveness that it gave her compared to her more timorous and fragile "normal" form. After her brief solo career, she joined The Avengers. This lead to her participation in the Secret Wars, most notable for sparking her long standing rivalry with the newly empowered Titania. After the Avengers, she temporarily replaced the Thing in the Fantastic Four.

During her tenure with the Fantastic Four, the She-Hulk had to prevent a radiation leak in a downed S.H.I.E.L.D. Helicarrier. This radiation exposure had a drastic effect on Jennifer: she could no longer transform back into her original form. However, this was an agreeable turn of events for her, since she preferred being She-Hulk, and it was revealed much later that the block was purely psychological.

In her She-Hulk form, Jennifer possesses immense superhuman strength. When she transforms back and forth, she gains/loses considerable mass (much of it muscle). Unlike her cousin, her personality and intelligence are less affected when she transforms into the She-Hulk, although she becomes more self-confident and assertive.

As She-Hulk, Walters is exponentially stronger than she is in her Jennifer Walters form. Additionally, any extra strength gained as Jennifer Walters through intense physical training will be amplified, making her She-Hulk form even stronger. She used this to her advantage to prepare for a fight with the Champion of the Universe on an alien world (where court cases were decided through boxing matches), and managed to defeat him. While Jennifer Walters' training resulted in her becoming a bit more toned, She-Hulk's musculature, in contrast, became much more pronounced. As a result, she donned a special strength-controlling bodysuit to replace her business clothes, which no longer fit her frame. Walters subsequently shed some of that muscle mass during a work hiatus, but since first becoming She-Hulk, her strength has increased. Although the She-Hulk's strength originally remained at a set level and did not increase, later in her history her strength increases as her anger grows, similar to her cousin the Hulk. However, Jennifer's strength does not reach the Hulk's rage-enhanced levels. During the Avengers story arc "The Search for She-Hulk", it was established that fear also increases her strength. She-Hulk is impervious to high levels of force, pain, and disease: her skin can withstand extremes of temperature, as well as tremendous stresses and impacts without puncture wounds or lacerations. Despite this, she has been proven to be highly ticklish, as she was once tickled by the Hulk Robot during a battle between a rag-tag group of villains and the Avengers during the Acts of Vengeance. Her enhanced physiology renders her immune to all terrestrial diseases. She-Hulk also possesses a healing factor, which enabled her to completely recover, within minutes, from a skewering by the Wendigo.

Thanks to training by the Ovoid alien race, She-Hulk can exchange her physical characteristics and powers with the physical characteristics and powers of another being by simply focusing on a mental image of the person and willing the transfer to take place. The actual intent of the Ovoid skill is to exchange the minds of the user and another being, but it was theorized by the Ovoid who trained the She-Hulk that some factor of her gamma-mutated physiology causes her use of this talent to manifest in a different way. She rarely uses this power; unless she initiates this exchange with another superhuman being, she will become basically human in ability, but still green-skinned and generally recognizable as She-Hulk, and thus vulnerable to attack (a fact that the super-villain Titania took advantage of the one time She-Hulk did use this ability).

She-Hulk's legal practice requires her to spend extended periods of time as Jennifer Walters. The Scarlet Witch cast a spell for her which rendered anyone intending to harm the She-Hulk incapable of recognizing her as Jennifer Walters. However, the spell actually rendered Jennifer Walters completely undetectable to these individuals. While this had its advantages, it also left Jennifer unable to communicate with certain people whose knowledge or information it was vital for her to acquire. The spell was eventually removed by Dr. Stephen Strange, the Sorcerer Supreme of the Marvel Universe.