In the quaint Brazilian village of Belo Quinto, a Jesuit priest named Father Andrew Kiernan, who previously dedicated his life to science, embarks on an intriguing investigation into alleged miracles. This quest leads him to a statue of the Virgin Mary that astonishingly weeps blood during the funeral of Father Paulo Alameida, a man who had previously experienced the profound stigmata. As Father Kiernan gathers evidence, a mischievous young boy pilfers a rosary from the deceased, selling it to a woman in the bustling marketplace. She then sends this rosary to her daughter, Frankie Paige, who resides in Pittsburgh.
Not long after receiving the rosary, Frankie finds herself under attack from an invisible force while in the bath, resulting in two deep wounds on her wrists. Despite medical examinations, doctors are baffled by the origins of her injuries. When Frankie encounters a priest, believing him to be Kiernan, she discovers instead that he is Father Derning. Her distress escalates when, during a train ride, lights flicker ominously as she is again whipped by the unseen force. Hospitalized once more, the priest shares video footage of her distressing episode with the Vatican, prompting a more rigorous investigation by Andrew.
Andrew soon interviews Frankie, suspecting that her injuries could indeed be stigmata. When she identifies herself as an atheist, he explains the significance of stigmata as a phenomenon experienced by those extraordinarily devoted, mirroring the five wounds of Christ on the cross. Intrigued, Frankie plunges into her own research. Her ordeal intensifies as she experiences a head injury, a third wound linked to the Crown of Thorns. In a moment of desperation, she flees home, only to encounter Andrew, who subsequently follows her into an alley. In a frantic outburst, Frankie shatters a glass bottle, using the shards to inscribe cryptic symbols on a car's hood, while yelling in an unknown tongue.
To further decipher her condition, Andrew takes Frankie to Father Derning's church, where scholars translate her words articulated in Aramaic. The next day, Andrew's return to her apartment reveals startling changes: Frankie is now scribbling in Aramaic across the walls. Her voice transforms to a male tone, where she unexpectedly speaks Italian, and fresh wounds emerge on her feet, indicating the fourth stigmatic injury. Following this shocking turn of events, Andrew sends images of Frankie’s writings to the Vatican, which triggers a series of alarming responses from church officials who recognize the significance of her inscribed words, believed to be content from a newly discovered gospel.
However, upon visiting Frankie's apartment once again, Andrew finds her messages painted over, and she turns aggressive, attempting to seduce him before violently rejecting his faith. In an eerie display of power, Frankie levitates and weeps blood, prompting her transport to another church under the watch of Father Houseman and Dario. At Father Derning's location, Andrew learns from Marion Petrocelli that Frankie's writings are components of a lost gospel, initially uncovered near Jerusalem but later suppressed by the Church due to its radical implications.
Petrocelli divulges that Alameida, who suffered from stigmata, had been conducting a translation of the document that posited the notion that the Kingdom of God resides within everyone, rather than being restricted to organized religion. Armed with this knowledge, Andrew races against time to where Frankie is under exorcism. In a chaotic confrontation, during which Houseman attempts to subdue Frankie violently, Andrew intervenes just as chaos erupts in flames around them. Embracing the risk, Andrew resolves to act as Alameida's messenger, directly confronting the spirit that possesses Frankie, and manages to brave the flames to rescue her, thereby compelling the spirit to depart peacefully.
Eventually, Andrew returns to Belo Quinto, discovering the original texts of the lost gospel hidden in Alameida's church. Just as the credits near, a narrative unfolds about the discoveries surrounding the Gospel of Thomas, revealing the Church's resolute decision to shun it, deeming it heretical.
