Adolescents and adults with autism spectrum disorder (ASD) experience difficulties with emotion regulation (ER), which has been associated with a host of co-occurring problems with mood, anxiety, and aggression. Although treatments targeting ER are available for individuals with ASD, there is a limited understanding of factors that lead to successful outcomes. The therapeutic alliance is considered important for outcomes in non-ASD samples; however, the process of alliance formation and its relation to treatment outcomes is unclear for clients with ASD. The present study aims to examine the trajectory of alliance formation across treatment, as well as examine whether alliance is related to treatment outcomes or specific within-person characteristics. Participants included adolescents and adults with ASD (n = 39, mean age = 15.28 years, age range = 12 to 21 years, 79.50% male) who completed a 16-week intervention designed to treat ER difficulties. Client-therapist alliance was measured at four timepoints throughout treatment using an observational measure of alliance and parents rated their child’s ER difficulties. Interrater reliability on observer-rated alliance was strong. Alliance formation significantly fluctuated throughout treatment. Overall alliance strength, as well as alliance early in treatment, predicted better treatment outcomes. Additionally, ASD symptom severity and co-occurring depression were related to alliance strength. The current study supports the importance of therapeutic alliance for clients with ASD and highlights a need for increased alliance formation during critical stages in treatment. Considerations for future research are discussed.