Previous research has shown that media violence exposure can cause desensitization to violence, which in theory can increase aggression. However, no study to date has demonstrated this association. In the present experiment, participants played a violent or nonviolent video game, viewed violent and nonviolent photos while their brain activity was measured, and then gave an ostensible opponent unpleasant noise blasts. Participants low in previous exposure to video game violence who played a violent (relative to a nonviolent) game showed a reduction in the P3 component of the event-related brain potential (ERP) to violent images (indicating physiological desensitization), and this brain response mediated the effect of video game content on subsequent aggressive behavior. These data provide the first experimental evidence linking violence desensitization with increased aggression, and show that a neural marker of this process can at least partially account for the causal link between violent game exposure and aggression.