In the small town of Pontypool, Ontario, former shock jock turned radio announcer Grant Mazzy (Stephen McHattie) encounters a woman lightly clothed on a heavy snow-filled morning, who startles him when he makes a stop in his car. When he calls out to her, she disappears into the darkness, repeating his words ominously and visibly disturbing him. When he arrives for his shift at the radio station he is accompanied by technical assistant Laurel-Ann Drummond (Georgina Reilly) and station manager Sydney Briar (Lisa Houle).
As the morning proceeds, Grant's tactics for his radio announcements garners ire from Sydney as Laurel-Ann tries to settle their differences. They get a report from their weather and traffic helicopter reporter Ken Loney (actually a man on a hill with sound effects like a helicopter) about a possible riot at the office of Doctor Mendez in Pontypool. What he describes is a scene of chaos and carnage, immediately grabbing Grant's attention and puzzling the women as their live wire has not gotten any word of this. After he is unexpectedly cut off, the group tries to confirm the report, but they are not able to find much as their witnesses are disconnected before they even make it to the airwaves. Ken calls back amid the chaos and manages to get one of the "infected" survivors to speak into the phone, the sound is completely inhuman, and the call is again cut off, this time by a startling transmission of garbled French that Laurel-Ann is able to translate. The translation coming in was garbled telling them not to use terms of affection, phrases that conflict, or the English language. Grant tries to force his way to leave the station after they are called in quarantine from the activities outside, not believing this is happening when a horde of people attempt to attack them and they block themselves in. Meanwhile, Laurel-Ann begins expressing erratic behavior, getting stuck on the word "miss" repeating it over, and over again, then she imitates the sound of a boiling kettle, ceaselessly singing its tune when Dr. Mendez (Hrant Alianak) enters the studio and they block themselves off from her.
He explains his theory that somehow a virus has found its way into human language, infecting certain words spoken. As he explains this, Laurel-Ann begins a series of increasingly violent slams against the sound booth's window, chewing off her own lip and splattering blood with each attack. Ken calls in again and Grant puts what he describes on the radio shortly before Ken also succumbs to this strange attack on the language. Soon Dr. Mendez also begins to feel the effects to the word "breathe" and the horde has broken in, attacking the sound booth as well. They record a diversion to lead the mob away, and Mendez surmises that it is only the English language that was affected before Grant and Sydney leave him alone in the booth. They are nearly killed when the recording fails and the mob returns, but Mendez successfully lures them away again. Having given up and in guilt over killing a little girl who had been infected, Sydney begins to succumb to the word "kill" but thinking back to the warnings they had received Grant successfully confuses the language, repeating "Kill is kiss" over and over again until the signs of illness wear off. Armed with knowledge on how to stop this, the pair go on the air, spouting several non-contradicting and confusing phrases to try and help their infected listeners, ignoring warnings from the authorities who are trying to get them off the air. As they count down from ten, Sydney joins Grant in the booth and they kiss. As the countdown finishes, the screen goes dark, leading the audience to believe they had died in the attack.
The scenes follow indicate that the infection quarantine failed as reports of people afflicted by the language virus start to rise, including the announcer of a news station whose words are heard over the credits. When that ends, the scene shifts to a radically different view a stylized black-and-white version of Grant and Sydney in what looks like a far-eastern atmosphere, hinting to the audience they did survive their ordeal
