Internet gaming disorder (IGD) is a social problem that cannot be ignored. Considerable research has shown that IGD can impede the healthy physical and mental development of adolescents. Based on positive youth development theory and stage-environment fit theory, the current study explored the mediating effect of depression and the moderating effect of gender to determine the association between positive youth development (PYD) and IGD. A sample of 1970 Chinese adolescents aged 11–18 years (1021 boys, 940 girls, and 10 unidentifiable individuals) completed questionnaires related to PYD, depression, IGD, and their background information. The results revealed that PYD negatively predicted IGD. After controlling for gender and age, this study found that depression mediated the relationship between PYD and IGD. Furthermore, gender moderated the relationship between depression and IGD. Boys with depressive symptoms were more likely to indulge in IGD than girls. This research contributes to a more thorough understanding of how PYD decreases the risk of IGD. These findings suggest that cultivating PYD attributes is a promising approach to prevent or reduce depression and IGD among adolescents in mainland China.