Research has shown a negative relationship between weight bias internalization (WBI) and general measures of health-related quality of life (QOL), such as the Short Form-36. Less is known about the impact of WBI on weight-specific domains of QOL. This study examined the relationship between WBI and weight-related QOL, as measured by the Impact of Weight on Quality of Life (IWQOL-Lite) scale. Participants were 178 adults with obesity [71.3% black, 87.6% female, mean body mass index (BMI) = 40.9 ± 5.9 kg/m2] enrolled in a weight loss trial testing the effects of lorcaserin on weight loss maintenance. At baseline, participants completed the Weight Bias Internalization Scale (WBIS), the IWQOL-Lite and the Patient Health Questionnaire (PHQ-9, to assess symptoms of depression). Total scores for the IWQOL-Lite and its five subscales (Physical Function, Self-Esteem, Sexual Life, Public Distress and Work) were calculated. Linear regression analyses showed that WBIS scores were associated with the IWQOL-Lite total score and all subscales above and beyond the effects of demographic variables, BMI, and depressive symptoms (beta values = -0.18 to -0.70, p values < 0.019). The relationship between WBIS and the IWQOL-Lite scales did not differ by gender or race. WBI was associated with mental and physical aspects of weight-related QOL in a predominantly black and female treatment-seeking sample of patients with obesity. Prioritizing the development of interventions to reduce WBI may be important for improving weight-related QOL.