剧情将回到2006年，白宫发现总统的机密文件遭到骇客入侵而召来了里昂所带领的特工团队，在搜查期间却突然停电，并遇到了丧尸袭击。另一方面，TerraSave员工克莱尔在某个国家支持难民时，从一名患有失语症的少年手中获得了一幅看似有人感染病毒的画，并以此为展开调查。 翌日，克莱尔为了修建福利设施的议题前往白宫，巧遇里昂并将少年的画展示给他看。尽管里昂认为白宫的丧尸事件和那幅奇怪的画有关联，克莱尔却持相反意见径自离去。两个遥远国家所爆发的丧尸事件，最终将发展成动摇国家的事态。

U.S. federal agent Leon S. Kennedy sneaks into the "East Slavic Republic" to verify rumors that Bio-Organic Weapons (BOWs) are being used in the country's civil war, which the U.S. and Russia are making preparations to jointly intervene in. Right after his infiltration, the U.S. government orders him to leave immediately. Determined to uncover the truth, Leon ignores the order and enters the battlefield to end the chain of tragedies caused by the BOWs.