This study aims to evaluate the relationship between social skills and sensory features, emotion regulation, and empathy in adolescents on the autism spectrum. One hundred and twenty-three adolescents were included in the study (50 autistic, 73 typically developing-TD adolescents). The participants filled out the Adolescent/Adult Sensory Profile (AASP) and Emotion Regulation Questionnaire. Parents of the participants completed the Child Empathy and Systemizing Quotient (EQ-C/SQ-C) and Autism-Social Skills Profile (ASSP) scales. Social reciprocity, social participation/avoidance, ASSP total scores, empathy and systemizing scores were lower, and detrimental social behaviors, low registration sensory profile scores were higher in the autism spectrum group. While a difference between genders was observed in sensory sensitivity, sensation avoiding, low registration quadrants and empathy scores, no gender and group interaction was found in any domain. Social skill total scores were correlated to sensation seeking and low registration sensory features, empathy, systemizing, and reappraisal emotion regulation scores. A hierarchical multiple linear regression analysis was conducted controlling for group and gender, sensation seeking (p = 0.032, [beta] = 0.138), low registration (p = 0.012, [beta] = - 0.215) of the AASP, and empathy (p < 0.001, [beta] = 0.555) and systemizing (p = 0.033, [beta] = 0.138) scores of the EQ/SQ-C was found to significantly predict social skill total scores. Although emotional regulation strategies may play a role, sensory processing features and empathy and systemizing skills seem to be the more significant contributors to social skills during adolescence. Interventions targeting sensory processing and especially improving empathy and systematization skills may positively affect social skills in adolescents on the autism spectrum.