Background: Substance abuse is one of the most common health outcomes associated with adverse childhood experience, and poses a significant public health threat. Objectives: The purpose of this study is to demonstrate a relationship between adverse childhood experience and a substance use disorder using nationally representative data as well as to test whether religion moderates this relationship. Methods: We conducted a secondary analysis using data from the National Longitudinal Study of Adolescent to Adult Health (n = 11,279). Three types of adverse childhood experiences were considered; physical, emotional, and sexual abuse. Logistic regression was used to determine whether risk for developing an alcohol use, cannabis use, or other drug use disorder in adulthood increased as exposure to multiple types of adverse childhood experiences increased while controlling for prior substance use and other demographic variables that have shown associations with substance use. In addition, religiosity was investigated as a possible moderator of the relationship between adverse childhood experience and substance abuse. Results: The likelihood of developing a substance use disorder later in life increased as the score on the adverse childhood experience index increased. While religiosity did significantly reduce the likelihood of developing a substance use disorder, no moderating effects were observed. Conclusions/importance: This study underscores the long-term consequences of exposure to childhood adversity.