Therapeutic alliance may influence treatment outcomes for individuals with autism spectrum disorder (ASD). The present study examined the trajectory of alliance, observationally-measured at four timepoints during a 16-week mindfulness-based treatment targeting emotion regulation problems in adolescents and young adults with ASD (n = 37, mean age = 15.28, 78.40% male). Variability in alliance as a function of client characteristics and the degree to which alliance predicted emotion regulation outcomes were assessed using parent-report forms. Results demonstrate that alliance fluctuates throughout treatment. Moreover, stronger alliance predicts decreased dysphoria at posttreatment. Results also suggest that increased ASD symptom severity and depression predict weaker alliance early and throughout treatment. Findings highlight a need for clinicians to consider the importance of developing strong alliance for clients with ASD.