Parental knowledge is a key protective factor for youths’ risky behavior. Little is known about how longitudinal combinations of knowledge-related behaviors are associated with youths’ substance use. This longitudinal study uses Latent Transition Analysis to identify latent patterns of parental knowledge-related behaviors occurring in mother-youth dyads during middle school and to investigate how changes in knowledge-related patterns are associated with youths’ substance use in Grade 6 and the initiation of substance use from Grade 6 to 8. Using a sample of 536 rural dyads (53 % female, 84 % White), we assessed mother and youths’ reports of parental knowledge, active parental monitoring efforts, youth disclosure, and parent-youth communication to identify six latent patterns of knowledge-related behaviors: High Monitors, Low Monitors, Communication-Focused, Supervision-Focused, Maternal Over-Estimators, and Youth Over-Estimators. Fifty percent or more of dyads in the High Monitors, Communication-Focused and Youth Over-Estimators were in the same status in both 6th and 8th grade: 98 % of Low Monitors in Grade 6 were also in this status in Grade 8. The initiation of alcohol, smoking, and marijuana was associated significantly with transitions between patterns of knowledge-related behaviors. The initiation of alcohol and smoking were associated with increased odds of transitions into the Low Monitors from the Communication-Focused, Supervision-Focused, and Maternal Over-Estimators. However, the initiation of substance use was associated with decreased odds of transitions from the High Monitors to the Low Monitors and with increased odds of transitions from High Monitors to Supervision-Focused. The discussion focuses on the value of using a person-oriented dyadic approach with multiple reporters to study changes in knowledge-related behaviors over the middle school period.