As the calendar transitions from March 1975 to August 1977, the world plunges into chaos following a devastating Sino-Soviet border conflict that unleashes biological warfare on humanity. Among the ruins of Los Angeles, U.S. Army Col. Robert Neville, portrayed by Charlton Heston, who is both a scientist and a medic, fights for his survival against the plague that decimates the population. In a desperate move to save his own life, he injects himself with an experimental vaccine, inexplicably granting him immunity.

Days turn to weeks, and as Neville roams the desolate streets, he becomes increasingly convinced that he is the last living person following this cataclysmic event. The memories of martial law and the swift deaths of countless people haunt him, fueling his resolve to destroy the Family—a vicious cult comprised of plague victims transformed into mindless and murderous mutants.

His nights are spent atop a fortified apartment building, a sanctuary riddled with tension, as the Family relentlessly seeks to breach his defenses, employing outdated siege tactics. When not under siege, they vandalize remnants of science, believing that technology is the root of all evil.

One day, while scavenging for clothing in a department store, Neville’s reality shatters as he sees a healthy woman among the debris. His brief pursuit yields no results, leading him to dismiss her appearance as a figment of his imagination—a momentary escape from his grim reality marked by the discovery of a Family member’s corpse, a chilling reminder of the plague’s eventual claim over all lives.

As the Family’s pursuit intensifies, they eventually capture Neville, condemning him to death after a cursory hearing led by Jonathan Matthias (a former news anchor). Tied to a giant wooden wheel—a symbol of modernity doomed to burn in Dodger Stadium—his fate seems sealed. However, an unexpected salvation arrives in the form of Lisa, a woman he thought was merely a product of his fevered imagination, alongside Dutch, a former medical student. Together, they are part of a small group of survivors under 30, who, despite their youth, are not fully shielded from the ravages of the disease.

Realizing the daunting reality of preserving humanity, Neville contemplates finding a way to duplicate the vaccine using his blood. This spark of purpose drives him to formulate a plan. Meanwhile, he and Lisa return to his apartment to help her brother, Richie, who is battling the disease’s grip. Their anticipation of a romantic evening is shattered when a generator fails, plunging them into darkness as the Family seizes the opportunity to attack.

During this chaos, Brother Zachary, trusted lieutenant of Matthias, manages to infiltrate Neville’s stronghold. Unaware of the lurking danger, Lisa’s life hangs by a thread as Neville risks everything to restore power. Upon his return, a harrowing scene unfolds—Zachary threatens Lisa, prompting Neville to act decisively, eliminating the threat before it’s too late.

With newfound determination, Neville creates a serum that successfully treats Richie, who, in gratitude, reveals the location of the Family’s stronghold—the Los Angeles Civic Center. However, he urges Neville to offer mercy to the Family, seeing their lingering humanity. This altruistic sentiment faces skepticism from Matthias, who views Richie as a spy and orders his execution, thrusting Neville into a desperate race to save his friend.

Arriving too late, Neville finds Richie dead, victim to Matthias’ cold calculations. A heartbroken Neville soon faces Lisa’s rapid decline into the Family, who betrays him by allowing Matthias and his followers access to his home. Confronting Matthias, Neville watches helplessly as the Family destroys his sanctuary.

Desperation consumes him as he breaks free, hoping to save Lisa, but Matthias proves too cunning, inflicting a mortal wound on him with Zachary’s spear. As dawn breaks, Dutch and the survivors discover Neville’s lifeless body, hauntingly positioned in a fountain alongside the precious blood serum he left behind.

With a weakened Lisa beside him, Dutch takes possession of the serum and leads the remaining survivors away from the ravaged city, leaving behind the grim ruins of their former existence.