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 and his dog Sam search the streets for food, use radio to find survivors, and study ways to cure the virus in the laboratory; at night, he can only hide in the house, because those people who are infected with the virus and do not die, become "night demons" who can only come out at night, lose their minds and attack all people. One day, Sam was also infected with the virus and died, and Robert Neville fell into unprecedented loneliness. When he is ready to die with the night demons, another survivor, Anna (Alice Braga), saves him. Anna believes there are survivors in the quarantine zone on the mountain, but the stubborn Robert Neville insists on staying in New York. Another night, the Night Devil attacked Robert Neville's residence, by which time his research had been successful, but only by holding on until dawn could humans survive.