After the outbreak of the T-virus initiated in Raccoon City, the whole world is destroyed and crowded with flesh-eating zombies, and the humans keep moving, fighting to survive. Alice travels alone in her motorcycle through the Nevada Desert, where she meets a convoy of survivors lead by Claire Redfield with Carlos Olivera and helps them to fight against a bunch of zombie-crows.

The group decides to travel to Las Vegas first to get fuel and supplies and then head to the decontaminated Alaska. Meanwhile, in an underground facility of the Umbrella Corporation, the evil Dr. Isaacs is researching an anti-virus to domesticate the zombies and cure people using clones of Alice. When Dr. Isaacs locates Alice through the satellite, he forges an order from the president and the troops chase Alice, while the group of survivors fights against a horde of zombies in Las Vegas.