Background: Various mental health and eating behavior variables have been independently associated with predicting weight loss in individuals with obesity. This study aims to investigate a mediation model that assesses the distinct contributions of these variables in predicting weight changes in patients with obesity following an outpatient behavioral weight loss intervention (BWLI). Methods: General mental health (depression, anxiety, stress, impulsivity), eating behavior (cognitive restraint, disinhibition, hunger), eating disorder pathology, and body mass index (BMI) were assessed in a group of 297 patients with obesity at the admission of a BWLI program. BMI was re-evaluated during the final treatment session. A mediation model was employed to examine whether mental health and eating behavior variables predicted BMI changes, with eating disorder pathology serving as a mediator. The model was tested both overall and within two patient subgroups: those with regular binge eating (≥four episodes/month) and those without. Results: In the overall sample (n = 238), the relationships between depression, impulsivity, and cognitive restraint with BMI change were mediated by eating disorder pathology. In the subgroup with regular binge eating (n = 99, 41.6%), the associations between stress and disinhibition with BMI change were additionally mediated by eating disorder pathology. In the subgroup without regular binge eating, eating disorder pathology showed no mediating effect. Discussion: Multiple mental health and eating behavior variables assessed at admission predicted BMI changes, particularly when mediated by eating disorder pathology in patients with regular binge eating. A comprehensive psychopathological assessment prior to starting BWLI may help identify multiple factors affecting prognosis and treatment outcomes. Long-term follow-up studies in this field are required.