Background: Obesity has serious psychosocial consequences for youth and family members and has reached epidemic levels in Portugal. Objective: This study had two goals: (1) to investigate differences in family cohesion, mothers' quality of life (QoL), and externalizing/internalizing symptoms between children/adolescents with healthy-weight and overweight/obesity; (2) to assess the mediating role of maternal QoL and children/adolescents' externalizing/internalizing symptoms in the association between family cohesion and weight. Methods: Children/adolescents with healthy-weight (n = 134) and with overweight/obesity (n = 163) and their mothers participated in the study. Mothers completed measures of family cohesion (FC) and QoL and children/adolescents completed measures of externalizing and internalizing symptoms. This study used a cross-sectional design. Results: Children/adolescents with overweight/obesity reported higher levels of externalizing and internalizing symptoms than children/adolescents with healthy-weight. Mothers of children/adolescents with overweight/obesity reported lower levels of FC and QoL than mothers of children/adolescents with healthy-weight. Mothers' QoL and children/adolescents' externalizing symptoms sequentially mediated the relationship between FC and weight status. Specifically, an increase in FC and QoL resulted in a decreased likelihood of the child/adolescent reporting overweight or obesity, whereas an increase in externalizing symptoms resulted in a higher likelihood of the child/adolescent reporting overweight or obesity. Conclusions: This study identifies mechanisms that might account for the link between FC and weight, suggesting the importance of mothers' QoL and children's externalizing symptoms. Moreover, it provides a better understanding of the psychosocial outcomes related to pediatric obesity, highlighting the relevance of working with the parents to promote weight reduction in youths.