Events of The Last of Us
James and David met Ellie when they ran into each other while hunting in the winter of 2033. When Ellie readied her bow, David offered to trade her some supplies for the deer meat she obtained to defuse the situation. She asked if they have any antibiotics, which they did. David ordered James to go and retrieve the medication, despite his concerns.
When he eventually returned with the medicine, he found Ellie holding David at gunpoint, and raised his pistol at her, having also learned from overhearing the previous conversation between the two that her and Joel were responsible for killing members of their group at the University of Eastern Colorado. David then insisted that he lower his gun and give Ellie the penicillin, to which he reluctantly complied. After stating that the other members of the group wouldn’t approve of letting her go, James angrily tossed over the medicine, and moved out of Ellie's way so that she could leave. He then told the group about Ellie's involvement in their friends' deaths.
When David sent men to track and catch Ellie, they decided to try and kill her instead because of what James told them. However, David personally captures Ellie himself and brings her back to their camp. Ellie awoke to find herself locked in a cage — she witnessed James chopping the limbs off of a human body. Upon seeing her cowering in fear, James scoffed and left to notify David. Having realized that David's group were cannibals, Ellie refused to cooperate. After a brief altercation, David ominously reiterated her own words, saying "[...] chop into tiny pieces." 
The following morning, James grabbed Ellie from her cell and helped David throw her onto a table, apparently intending to kill and harvest her, with James pinning her down so that David could chop her head with a meat clever. Ellie then abruptly declared that she was infected, and stated that David was infected too, having bit him before she was thrown onto the table. David was initially skeptical, but Ellie insisted that he roll up her right sleeve to show him her bite wound. Upon seeing this, James became frightened and apprehensive, but David insisted that Ellie’s bite must have not been real, as, if it was, she would have turned sooner. Panicked and repulsed, James became distracted and weakened his grip on Ellie's left hand as David began to observe his bite from Ellie. Taking advantage of their distraction, Ellie grabbed the butcher knife, and thrust it into James' neck, killing him.
Later, when confronting Ellie at the restaurant, David told Ellie that he wished she hadn't killed James, mentioning that James was just trying to do what he was told.
James was implied to be David's right-hand man and is a cannibal like David and his group. David personally views the man as his friend. Unlike David, James was not seemingly as kind-hearted and does not always agree with his decisions. Knowing that a group of David's men were killed in the University by a crazy man and a little girl, he overheard David's conversation with Ellie about the incident and was reluctant to let Ellie leave, but complied none the less; one of the few cannibals to do so. It also appeared that he knew David was putting on a facade towards Ellie by how the man was so calm and let her go.
When James notices Ellie waking up, he informs David straight away. James appeared to work for David at times, butchering a human corpse for him and the group. He also assisted him in their attempt to butcher Ellie, demonstrating David's reliance on him. He even went out hunting with David, displaying a gesture of protection when Ellie threatened him.
When James was killed by Ellie, David indicates sadness for his death, saying that James was just trying to do his job, and Ellie shouldn't have killed him.
James and Ellie immediately had an extremely hostile relationship with one another, with Ellie initially being distrustful of James and ready to kill him if need be. When the two first met, she even mockingly called him "Buddy-Boy".
Once James discovered that Ellie killed many of his friends at the University of Eastern Colorado, he held her at gunpoint, stating that she shouldn't be allowed to live after what she and Joel did to their group. James' anger towards Ellie was only withheld by his loyalty to David, as he obeyed the latter's orders to lower his gun and give her the penicillin, albeit with reluctance.
James' hatred of Ellie was shown to be quite strong, as he appeared very eager to hold her down so that David could butcher her with a cleaver's knife. When Ellie announced that she was infected and capable of spreading the infection to others, James expressed fear and hesitated to keep her restrained. However, this led to Ellie taking advantage of the opportunity to escape and wound up hacking his neck with a cleaver, killing him.