Childhood and adolescence are pivotal developmental stages for psychological health. An understanding of psychological mechanisms related to well-being is important for promoting positive life outcomes for youth. Research generally shows that the basic psychological need for autonomy is significantly associated with well-being. To examine the magnitude and sources of variation in this relationship, we conducted a meta-analysis of 90 reports to analyze the average effect of autonomy need satisfaction (ANS) and frustration (ANF) on indicators of psychological well- and ill-being for K-12 (Kindergarten to 12th grade) youth. Results indicated that ANS was positively associated with psychological well-being and negatively associated with psychological ill-being among youth. Further, ANF was negatively associated with psychological well-being and positively associated with psychological ill-being. Moderator analyses indicated that the association between ANS and well-being was stronger for studies conducted with children and adolescents in East Asian countries compared to studies conducted in the USA, Canada, or Northern Europe when controlling for publication status and measurement reliability. Results also showed that the average correlation between ANS and well-being was stronger for studies located in more collectivistic countries compared to individualistic countries when controlling for publication status and measurement reliability. The relationship between ANS and ill-being was stronger for studies conducted in the USA and Canada compared to East Asian and European contexts. Together, results suggest that autonomy satisfaction is related to the well- and ill-being of youth across cultural contexts, but that there is cultural variation in the association between experiences of autonomy and well-being.