Lawyer Erin Bruner defends a priest, Father Richard Moore, who is charged in connection with an exorcism that lead to the death of Emily Rose. The trial begins with the calling of several medical experts by the prosecutor, Ethan Thomas. One expert testifies that Emily was suffering from both epilepsy and psychosis. The defense contests that she may have actually been possessed, though Bruner is careful never to say that in so many words. Indeed, Bruner explains that Emily was suffering from something that neither medicine nor psychology could explain, and that Moore as well as her family realized this and tried to help in another way. Several flashbacks show how this began.
In a flashback, Emily's ordeal is shown. Alone in her dorm room one night, at 3:00 AM, Emily notices a strange burning smell coming from the hallway. When she checks on it, she sees the door open and shut by itself several times. When she goes back to her room, she sees a jar of pencils and pens move by itself. Additionally, her bedclothes roll themselves down and a great weight seems to press down on her, a force which also proceeds to choke her. Through these episodes, she wonders if they are really happening or if they are just hallucinations. She suffers more visions, is hospitalized, and diagnosed with epilepsy. She is given anti-seizure medications, which she claims do not work. Her visions continue, as do her severe bodily contortions.
She leaves school and returns to live with her parents. She and her parents become convinced she is neither epileptic nor mentally ill, but is possessed by demons. They ask for their local parish priest to be called in to perform an exorcism, and the Church agrees. The prosecution argues that all this could be explained by a combination of epilepsy (the contortions) and psychosis (the visions).
As the trial proceeds, Bruner begins to experience strange occurrences in her apartment at 3:00 AM, including strange smells and sounds. Moore warns her that she may be targeted by demons for possibly exposing them. Later in the film, he explains that 3:00 AM is the "devil's hour," which evil spirits use to mock the Holy Trinity. Significantly, it is the opposite of 3:00 PM, traditionally taken to be the hour at which Jesus died.
Seeing that the prosecution is putting up a seemingly solid medical case, Bruner decides to try to show that Emily may have actually been possessed. She calls in Dr. Sadira Adani, a professor in anthropology and psychiatry, to testify about various cultures' beliefs about spiritual possession. Adani quotes Carlos Castaneda's A Separate Reality as means to understand the subject, and suggests that Emily was a hypersensitive. Thomas objects, and dismisses the testimony as pseudoscience.
Dr. Cartwright, a medical doctor present during the exorcism, comes forward to reveal an audio recording made during the rite. Moore is then called to the stand to testify. The recording is played, and the film then flashes back to the exorcism. It is performed on Halloween night, because Moore believes it might be easier to draw out the demons on that night. Emily breaks her ties and jumps out a window, running into a barn. They follow her, and inside the barn, they are subjected to such phenomena as unnatural gusts of wind and demonic screams and voices. The demon inside Emily refuses to name itself after repeated demands from the presiding Father, but finally reveals contemptuously that there are not one but six demons. They go on to identify themselves in dramatic fashion, naming themselves one after another in dual voices from Emily. They identify themselves as the demons who possessed Cain, Nero, and Judas Iscariot, as well as the demons Legion, Belial, and Lucifer himself. Each manifests himself in corresponding native language: Hebrew ("אני הוא ששוכן בתוך קין", Ani hu sheshokhen betokh Cain, I am the one who dwelt within Cain), Latin ("Ego sum qui (in?)habitavit in Nerone", I am the one who inhabited Nero), ancient Greek ("ενοίκησα πάροιθεν εν Ιούδαι", enoikesa paroithen en Iouda, I dwelt before within Judas), German ("Und ich [war] mit Legion", And I was with Legion) and Aramaic (ܐܢܐ ܒܠܝܐܝܠ,Ana Belial, I am Belial) consecutively. Emily then finally utters in English "And I am Lucifer, devil in the flesh".
Bruner calls Moore back to the stand the next day. He reads a letter that Emily wrote before she died. In the letter, Emily describes another vision she had the morning after the exorcism. She walks out of the house and experiences a Marian apparition, in which she is told that although the demons will not leave her, she can leave her body and end her suffering. However, the apparition goes on to say that, if Emily returns to her body, she will help to prove to the world that God and the devil are real. Emily chooses to return, concluding the letter by saying: "People say that God is dead. But how can they think that if I show them the devil?" She then receives stigmata, which Moore believes is a sign of God's love for her. Thomas counters that she could have incurred the wounds by self-injury.
Father Moore is ultimately found guilty; however, on a recommendation from the jury, the judge agrees to a sentence of time served. Bruner is offered a partnership at her firm, but she refuses and instead, she resigns. She goes with Moore to Emily's grave, where he has put a quote (which Emily recited to him the night before she died) from the second chapter twelfth verse of Philippians on her grave: "Work out your own salvation, with fear and trembling."
