School inclusion of students with Autism Spectrum Disorder (ASD) is still a research challenge. Promoting school inclusion notably requires the understanding of cognitive underpinnings of ASD related limitations in school adaptive behaviors. More, such knowledge might provide relevant intervention’s targets for fostering school inclusion of youths with ASD. Our study aimed at exploring the relationships between school-related adaptive behaviors and cognitive functioning in youths with ASD according to the distinction of general (IQ, age) and specific cognitive factors (social-emotional skills, executive functions). Forty-five participants were recruited in specialized classrooms, including 27 with ASD (mean age = 14.26), and 18 with intellectual and/or learning disability (non-ASD) (mean age = 14.17). The participants, their parents and/or the specialized teachers answered to a set of tests measuring the cognitive functioning, school-related socio-adaptive behaviors and quality of life. After group comparisons on each measure, we performed multiple regression analyses for determining whether general and/or specific cognitive factors may predict school-related socio-adaptive behaviors and quality of life, which constitute hallmarks of school disability. Both groups exhibited equal performances on socio-emotional and executive measures. By contrast, youths with ASD showed more difficulties in socio-adaptive behaviors than youths in no-ASD group. Regression analyses revealed a single strong contribution of socio-emotional skills for predicting such limitations in the ASD group, while IQ and age were the best contributors in the non-ASD group. The low quality of life reported in both groups was slightly predicted by executive performances. These results emphasized the critical role of socio-emotional skills in the socio-adaptive functioning of youths with ASD at school, as well as the role of executive functioning in school-related quality of life.