Although clinically significant symptoms of anxiety or depression are present in nearly one in two people with autism spectrum disorder (ASD), little is known about how these symptoms may relate to social motivation, a key construct in the etiology of ASD. The aim of the current study was to examine patterns of anxiety, depression, ASD symptomatology, and social motivation in youth with ASD. Using a large public dataset of well-characterized youth with ASD (N = 195), we examined varying patterns of these symptoms via latent profile analysis (LPA). Three distinct classes emerged: one with moderate ASD severity and low levels of comorbid psychopathology, a second with more severe ASD symptoms and similarly low anxiety and depression, and a third with significantly elevated anxiety and depression. Neither sex nor age differed significantly among these classes, and indices of social interest early in development did not predict class membership. Implications of these symptom patterns for assessment and treatment of comorbidity in ASD are discussed.