Marathon Infinity takes the closed universe of the Marathon series and blows it wide open. The solo/co-op campaign, “Blood Tides of Lh’owon,” is a 20-level scenario sporting new textures, weapons, and aliens. More than that, the scenario sheds a surprising new light on the story’s characters and the meaning of events. Having defeated the Pfhor and reawakened the ancient remnants of the S’pht, the player now faces a world where friends become enemies and all is not what it seems…

The story in the single-player version of Marathon Infinity, titled "Blood Tides of Lh’owon", is not told in an explicit fashion. The narrative begins as if large parts, if not all, of the events in Marathon 2 had not happened. At the end of Marathon 2 proper, as the Pfhor's Trih Xeem or "early nova" device is fired upon the S'pht System's sun to explode it, Durandal recounts an ancient S'pht legend in which a chaotic entity known as the W’rkncacnter — an eldritch abomination — was sealed inside of that sun by the Jjaro — a highly advanced race from centuries past, their technology being the only remnants of their existence — eons ago. The story involves the player "jumping" between alternative realities via surreal dream sequences, seeking to prevent the W’rkncacnter from being released from Lh'owon's dying sun. These jumps are apparently caused either by technology left behind by the Jjaro or by the W’rkncacnter's chaotic nature. The player begins as Durandal's ally, only to be transported almost immediately to a reality where Durandal did not rescue the player at the end of the first game, Marathon; as such, he is controlled by the Pfhor-tortured AI Tycho instead.