Background: Adults with intellectual disability (ID) are at high risk of exhibiting challenging behaviors, especially those with autism spectrum disorder (ASD). There are clinical and transdiagnostic variables that are largely related to the existence of these behaviors, and it is necessary to know the particularities of their role in people with ASD and ID relative to those without ASD. Method: Eighty adults with ID and 83 with an additional ASD diagnosis participated in the study. We analyzed answers provided by their therapists to different measures of challenging behavior. Results: For the ASD population, emotional reactivity stood out as a predictor of self-injury, aggression and stereotypy. In the non-ASD group, the role of executive functioning and working memory were significant predictors of aggression and stereotypy was significant. Conclusions: Interventions aimed at the reduction of challenging behaviors in adults with ID should consider these variables to adjust to the needs of these individuals, mainly from a preventive perspective.