In 2012, humans were infected by an unknown virus, and New York became an empty city. Robert Neville (Will Smith) is a scientist serving the military and a survivor who is immune to the virus. During the day, he takes his dog Sam to look for food on the streets, uses the radio to find survivors, and studies ways to cure the virus in the laboratory; at night, he can only hide in the house, because those who are infected with the virus but not dead become "night demons" who can only come out at night, lose their minds, and attack everyone. One day, Sam also died of the virus, and Robert Neville fell into unprecedented loneliness. When he was about to die with the "night demons", another survivor Anna (Alice Braga) saved him. Anna believed that there were still survivors in the quarantine area on the mountain, but the stubborn Robert Neville insisted on staying in New York. Another night, the "night demon" attacked Robert Neville's residence. At this time, his research had been successful, but only by persisting until dawn could humans survive.