Destroy All Neighbors follows William Brown (Jonah Ray Rodrigues), a frustrated recording engineer with a dream of composing an epic prog-rock album. William’s determination is stymied by his new neighbor, Vlad (Alex Winter), an unbelievably loathsome and hideously loud lunatic. Vlad's horrifying noises and loud music drive William mad. He loses his girlfriend. He loses his job. And then, he loses his mind. William decides to confront Vlad and in the course of the argument accidentally kills him. Vlad’s severed head returns determined and taunt and belittle William. One accidental death of people in William’s life leads to another. William soon finds himself surrounded by the ghosts of his murdered victims. William’s deranged journey of self-discovery leads to him enlist the help of the undead neighbors to finish recording his prog-rock album.