© 2016, Springer International Publishing Switzerland. Purpose: Examine whether unhealthy and extreme weight control behaviors (WCBs) mediate the relationship between youth weight status and disease-specific health-related quality of life (HRQOL) in treatment-seeking youth who are overweight and obese (OV/OB). Method: 82 youth 10–17 years of age who were OV/OB and attending an outpatient obesity-related medical appointment completed measures assessing unhealthy and extreme WCBs and disease-specific HRQOL. Parents completed a demographic questionnaire and medical staff measured youth height and weight. Results: Regression analyses revealed that unhealthy WCBs mediated the associations between youth weight status and emotional and social avoidance disease-specific HRQOL, such that higher body mass index (BMI) predicted unhealthy WCBs, which were ultimately associated with poorer emotional and social HRQOL. Mediation analyses were not significant for total, physical, teasing/marginalization, and positive attributes disease-specific HRQOL. In addition, extreme WCBs did not mediate the association between youth weight status and any subscales of the disease-specific HRQOL measure. Discussion: Weight status is an important predictor of disease-specific HRQOL in OV/OB youth; however, the association with emotional and social HRQOL is partially accounted for by youth engagement in unhealthy WCBs. Clinicians and researchers should assess WCBs and further research should explore and evaluate appropriate intervention strategies to address unhealthy WCBs in pediatric weight management prevention and treatment efforts.