Beyond the immediate plot found by following the team's progress in their competition, Murderball also includes insight into the lives and thoughts of the members of the team, who are introduced to the audience as the overarching sports story continues. One of the original team members, Joe Soares, discusses the effects that led to his leaving the American team, despite being one of the highest-ranking performers in the sport. As he did not make the final cut for the US competing team, Soares went over to become the lead coach for the Canadian quadriplegic rugby team. This instigates one of the major conflicts in the film, the intense competition between Team US and Team Canada, a rivalry only compounded by Soares' defection from his country of origin.
Over the course of the film, the documentary follows as the team makes it all the way to the 2004 Paralympics. However, one of the final, most touching focuses is as the sport not only leads Soares to realize that his family is really what is most important to him, but also helps a young man named Kevin begin to come to terms with his disability. At the end of the film, Mark Zupan, a central figure from the US team, shows how quadriplegic rugby can continue to empower a new generation.