The high prevalence of Internet gaming disorder (IGD) among Asian youth indicates an urgent need to identify protective factors and examine their consistency across Asian cultures in order to facilitate cost-effective interventions. Based on the transactional theory of stress and coping, this study collected data of 1243 online gamers (45% males; 18–25 years) through an anonymous survey from universities in China and Japan and investigated whether three coping resources (i.e., mindfulness, coping flexibility, and social support) serve to protect Chinese and Japanese youth from the impact of psychological distress on IGD tendency. After adjusting for the measurement non-invariance across samples, we found that Japanese students reported higher levels of IGD tendency and psychological distress than Chinese students. The results of multiple-group SEM analyses showed that, after controlling for other predictors, mindfulness served as the strongest protective factor against IGD across samples. Moreover, the buffering effect of mindfulness on the association between psychological distress and IGD tendency of female (but not male) students was observed. Our findings highlighted the cross-cultural invariance of the impact of psychological distress and coping resources on IGD in Chinese and Japanese youth, which can be considered in future IGD prevention programs.