An otherworldly parasitic alien species escapes its dying home planet and lands on Earth, adopting the form of small seed pods adorned with pink blossoms.
Elizabeth Driscoll, a dedicated laboratory scientist at the San Francisco Health Department, unwittingly brings one of these peculiar flowers home, sharing it with her boyfriend, Geoffrey. However, when she awakens the following day, she is taken aback to find Geoffrey acting strangely cold while disposing of the shattered glass that once housed the flower pod.
Worried about Geoffrey's unsettling transformation, Elizabeth confides in her colleague and close friend, Matthew Bennell. She expresses her fear that Geoffrey might no longer be the same person. Elizabeth even follows him secretly, observing meetings with unfamiliar individuals. Seeking guidance, Matthew suggests she consult with his psychiatrist friend, David Kibner, which she reluctantly agrees to.
As they make their way to Kibner, a panicked man, chased by a mob, warns Elizabeth and Matthew of impending danger. Intrigued, the couple follows the mob only to discover the man's lifeless body, surrounded by a group of emotionless onlookers. At Kibner's book signing event, Matthew reunites with his friend Jack Bellicec, an aspiring writer, while Elizabeth meets Kibner, who comforts a woman expressing fears that her husband has changed. Kibner dismisses their concerns with a wave of his hand, attributing the behavior to mere lack of commitment, which reinforces Elizabeth's worries about Geoffrey.
Puzzled, Elizabeth returns home, and Jack heads back to the mud bath spa he operates alongside his wife, Nancy. The couple stumbles upon an uncanny embryonic body that resembles Jack, compelling them to call Matthew. When Matthew arrives and witnesses the disturbing scene, he rushes to alert Elizabeth, only to find a near-complete replica of her in the bedroom. In a moment of urgency, he rescues Elizabeth and tries to inform the police and Kibner, but by the time they arrive, the duplicates of Jack and Elizabeth have vanished without a trace.
Elizabeth becomes increasingly suspicious of the flowers' role in this bizarre turn of events but is unable to examine one at the health department. Matthew struggles to alert the authorities to the bizarre happenings. After encountering multiple doppelgängers, Matthew, Elizabeth, Jack, and Nancy barricade themselves in Matthew's apartment. They ring Kibner, who promises assistance but later drives off with a group of duplicates, casting doubt on his intentions. As the group drifts off to sleep, giant flower pods start emerging in the garden, leading to the chilling realization that their replacements are being birthed.
Matthew manages to destroy his own duplicate just in time, but soon they find themselves relentlessly pursued by the "pod people"—the fully-formed alien replicas. Jack and Nancy bravely create a diversion, which leads to their tragic sacrifice, allowing Matthew and Elizabeth to escape to the health department. There, they take stimulants to stave off sleep, desperately trying to resist the encroaching threat posed by Kibner's duplicitous counterpart, who explains the aliens' nefarious plan to replace humanity entirely.
In a tense standoff, Matthew vanquishes Jack's double and confines Kibner's duplicate in a freezer before escaping with Elizabeth. They find Nancy, who cleverly pretends not to feel emotions, blending in among the duplicates, but this charade is short-lived when Elizabeth sees a horrific dog-human hybrid — a tragic outcome of a flawed pod — and screams, which alerts the pod people with their piercing cries.
In the chaos, Matthew and Elizabeth lose Nancy. Climbing aboard a truck filled with plants for Pier 70, they uncover a warehouse bustling with alien pods. While Matthew investigates a nearby ship, leaving Elizabeth—whose ankle is hurt—behind, he returns only to find her asleep. In a heart-stopping moment, he attempts to rouse her, but she disintegrates into nothingness as her duplicate emerges from the grass. Enraged and horrified, Matthew flees, breaking into the warehouse to burn the place down, annihilating numerous pods and killing many of the alien invaders. He conceals himself beneath the pier as the hunters search for him, fully aware that he cannot last much longer without sleep.
Time passes, and Matthew finds himself in the health department, now acting emotionless like the other duplicated employees. Emerging outside, he encounters the genuine Nancy, who misjudges him for one of them. Gripped by dread, she realizes the truth when he points at her and emits the eerie, high-pitched scream of the duplicates.
