When a virus causes a large portion of humanity to become uncontrollably violent, Deacon, his wife Sarah (Courtnee Draper), and his friend Boozer (Jim Pirri) attempt to flee for safety. However, Sarah is stabbed and critically wounded, forcing Deacon to evacuate her on a National Emergency Response Organization (NERO) helicopter. Due to the helicopter being at capacity, Deacon stays behind with Boozer, intending to reunite with Sarah.
Two years later, civilization has collapsed and large hordes of the infected, now called “Freakers”, roam the landscape and are a persistent threat to surviving humans. Deacon and Boozer now work as freelance bounty hunters in what’s left of Oregon, with Deacon believing Sarah is dead after finding out the NERO refugee camp she was evacuated to was overrun by Freakers. Deacon and Boozer plan to head further north to find better opportunities, but Boozer has his arm badly burned by a gang of cultists called Rippers, forcing him to stay at their safehouse to recuperate and delay their trip. Deacon also learns the Rippers have placed a price on his and Boozer’s heads. In addition, Deacon catches sight of NERO helicopters carrying a research team several times, leading him to believe there is a chance Sarah may be alive. He manages to track down and confront one of the NERO researchers, O’Brian, who evacuated Sarah. He reveals that his helicopter was diverted to a different camp mid-flight, rekindling Deacon’s search.