The story opens in a diner at the Kansas state line. Carnage has escaped from captivity and continues his murderous rampage here. Later that day in New York City Deadpool is watching TV and a news story about Carnage's rampage at the Kansas diner comes on. He decides he is the perfect crazy person to hunt down another crazy person and off he goes in search of Carnage. He finds him at an abandoned farmhouse near Tulsa, Oklahoma and proceeds to try and take him down. As he's about to deliver the coup de grace a new combatant, Shriek, stops him.
The story resumes at the Tulsa area farmhouse with Carnage and Shriek continuing to put the smack down on Deadpool. Deadpool pulls another trick out of his bag and forces Shriek and Carnage to retreat which is good since Deadpool is worked over as well. The three find themselves on the same interstate and battle between Carnage and Deadpool picks up where it left off. Round two!
The story resumes with Carnage definitely winning round 2 and leaving Deadpool on the interstate looking more like a pound of ground beef than anything else. Carnage grabs Shriek, who was injured at the start of the battle, and proceeds to car jack a family filled minivan and heads off in search of a sign. Deadpool eventually finds Carnage's trail at an old ghost town. Turns out there's a secret military base under this ghost town though and Deadpool heads underground looking for Carnage and Shriek. He finds them and gets worked over good. He recovers a little differently than usual.
Carnage invades an insane asylum looking to get some answers from some fellow crazy folk. Deadpool catches up to him here and thanks to the symbiotes that merged with him at the secret base he is able to separate Carnage and Shriek allowing him to fight them one at a time. Carnage begins to question his modus operandi. After incapacitating Deadpool he wanders off to think. Deadpool finds Shriek and makes sure she's no longer a problem. Carnage stumbles on her body and this turns out to be the final straw that causes him to stop his rampage and voluntarily incarcerate himself.