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Anxiety and depression are prevalent among autistic adolescents and may be difficult to accurately diagnose and treat given various factors (e.g., diagnostic overshadowing, heterogeneity). Therefore, efforts to examine transdiagnostic factors (i.e., distress tolerance, behavioral activation) may afford more parsimonious means for assessment and treatment. To our knowledge, there has been little research on distress tolerance, behavioral activation, and depressive and anxiety symptoms in autistic adolescents to guide diagnostic practices and treatment planning. In the current study, we examined the interrelationships between these transdiagnostic factors and depressive and anxiety symptoms using ratings from 100 verbally fluent autistic adolescents without intellectual disability (M age  = 13.70, SD age  = 2.23, Range: 11:00-17:11 years) and 100 of their caregivers. Many adolescents reported male sex assigned at birth (61%), cisgender (87%), not Hispanic/Latinx (90%), and White (80%) identities. A series of correlational analyses were employed to examine associations between these constructs from youth and caregiver perspectives, and multiple linear regression analyses were conducted to explore the mediating roles of distress tolerance and behavioral activation. Preliminary results show that low distress tolerance and behavioral activation were associated with more severe internalizing symptoms per self- and caregiver-report. Some differences by rater emerged, which highlight the importance of multi-informant ratings in autism. Results from mediation analyses may show that behavioral activation may be more salient to assessments and treatment planning for depression than distress tolerance, while distress tolerance may be important for both anxiety and depression; however, findings are preliminary given the cross-sectional nature of the data. Findings suggest that these transdiagnostic concepts may be important to individualizing treatment approaches, including the timing of certain approaches, for anxiety and/or depression in autistic adolescents., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)