Higher rates of depression and of depressed mood are associated with autistic traits, and both are associated with social interaction factors, such as social self-efficacy, social motivation and loneliness. This study examined whether these social factors explain the association between autistic traits and depression. 658 participants’ data were collected via an online survey. A mediation analysis found the relationship between autistic traits and depressive symptoms was fully mediated by the other three factors, forming a pathway from autistic traits, to social self-efficacy, to social motivation, to loneliness and finally to depressive symptoms. These results suggest that targeting social self-efficacy may break this pathway and disrupt this relationship. Interventions targeting supporting positive social interaction should be considered.