This nonexperimental study used mixed-effects regression models to examine relations among supervisor adherence to a clinical supervision protocol, therapist adherence, and changes in the behavior and functioning of youths with serious antisocial behavior treated with an empirically supported treatment (i.e., multisystemic therapy [MST]) 1 year posttreatment. Participants were 1,979 youths and families treated by 429 clinicians across 45 provider organizations in North America. Four dimensions of clinical supervision were examined. Mixed-effects regression model results showed that one dimension, supervisor focus on adherence to treatment principles, predicted greater therapist adherence. Two supervision dimensions, Adherence to the Structure and Process of Supervision and focus on Clinician Development, predicted changes in youth behavior. Conditions required to test hypothesized mediation by therapist adherence of supervisor adherence effects on youth outcomes were not met. However, direct effects of supervisor and therapist adherence were observed in models including both of these variables.