High functioning adolescents with Autism Spectrum Disorder (ASD) often have adjustment difficulties, specifically loneliness and depression. To better understand contributing factors, the current study evaluated associations between several Executive Function (EF) domains, social impairment, and friendship quality on depressive symptoms and loneliness in this population. Participants included 127 high functioning ASD adolescents and a parent/caregiver. Results indicated significant levels of parent-reported EF impairment which were positively correlated with increased levels of loneliness and depressive symptoms. Social impairment was identified as a significant mediator between all studied EF domains and adjustment, while friendship quality only partially mediated the relation between emotional control and loneliness. These results have implications for treatments focusing both on social skills and adjustment in adolescents with ASD.