Father Philip Lamont, portrayed by Richard Burton, is a troubled priest grappling with his faith as he endeavors to exorcise a possessed girl from South America living in the impoverished areas of Rio de Janeiro. This girl, claiming to possess the ability to "heal the sick," ultimately meets a tragic fate when she self-immolates.
Upon returning to Vatican City, Lamont finds himself tasked by the Cardinal to look into the mysterious death of Father Lankester Merrin, who was killed four years earlier while attempting to perform an exorcism on the Assyrian demon Pazuzu, possessing Regan MacNeil. The Cardinal reveals that Merrin is facing posthumous heresy charges for his controversial writings, which the Vatican wishes to disavow in light of its modernizing stance on the existence of evil.
Meanwhile, Regan, once the centerpiece of a notorious incident, now resides with her guardian Sharon Spencer in New York while her mother is away filming. Although she insists she remembers nothing of the traumatic events in Washington, D.C., her psychiatrist, Dr. Gene Tuskin, suspects that her memories are merely repressed. Lamont attempts to gain insights from Regan but finds his efforts thwarted by Tuskin, who believes his probing would be detrimental. To delve deeper into Regan's past, Tuskin uses hypnosis, linking herself with Regan through a biofeedback device called a "synchronizer."
After a briefing at the Georgetown house where the exorcism took place, Lamont is linked to Regan through the device and is transported back in time by Pazuzu to witness Father Merrin exorcising a boy named Kokumo in Africa during the 1930s. This journey reveals that Kokumo possesses unique abilities to combat Pazuzu, who manifests as a swarm of locusts. Determined to seek Kokumo, now portrayed by James Earl Jones, Lamont disregards the orders of his superiors and travels to Africa.
While Lamont explores the nature of Pazuzu's attacks—which target individuals with psychic healing abilities—Kokumo has become a scientist investigating means to prevent grasshoppers from turning into locust swarms. Back in the United States, Regan exhibits her telepathic gifts, even aiding an autistic girl in finding her voice. Father Merrin had believed that such psychic abilities were spiritual gifts heralding a new age of global consciousness, with Regan and Kokumo as the precursors of this transformation. In a visionary encounter, Merrin implores Lamont to protect Regan.
Upon arriving back in New York, the duo returns to the Georgetown residence, accompanied by Tuskin and Sharon, who remain vigilant of Regan's safety. During their journey, Pazuzu tempts Lamont with the prospect of boundless power, taking on the guise of a seductive doppelganger of Regan. Initially giving in to temptation, Lamont is eventually pulled back to reality by the real Regan, leading to a confrontation with the demon in its tempting form amidst a cascading swarm of locusts that wreaks havoc upon the house. Despite the chaos, Lamont triumphs over the doppelganger, tearing its heart from its chest.
In an act of defiance, Regan manages to banish Pazuzu and the locusts, employing a ritual that Kokumo had previously failed to execute. While the confrontation unfolds, Sharon succumbs to her injuries from self-immolation. Dr. Tuskin advises Lamont to keep a watchful eye over Regan as they depart, leaving the doctor behind to field inquiries from the authorities about the shocking events that have just transpired.
