Three elderly women-Mildred, Essie, and Dora-are hyper-religious zealots who believe they have been called to keep their church free from sin and corruptibility, all the while not realizing they are the ones who are corrupt.

Using scripture to support their cause, their misappropriation and misinterpretation of the Biblical text launches them on a mission of cleansing the flock-that is, killing whomever they think is evil and displeasing to the Lord. Rooted in misunderstanding, misdirection, and murder, the story of Church Ladies unfolds as Mildred, the ringleader of the group and the most disturbed of the three, is interviewed by a reporter while serving a life sentence in prison.