We tested the effects of emotional eating in long-term weight-loss so that both treatment processes and theory could be improved. Women with obesity participated in treatments of either high interpersonal contact and behavioral methods (n = 39) or low interpersonal contact and educational methods (n = 36) through community-based settings. We assessed mood, emotional eating, self-regulation, self-efficacy, and weight. Changes in the psychosocial measures were significantly greater in the high interpersonal contact/behavioral methods group. That group had a mean weight reduction of 6.5% and 6.8% over 6 and 24 months, respectively, which was significantly greater than the 2.9% and 1.8% loss in the low interpersonal contact/educational methods group at the same time points. Using aggregate data, change in eating self-regulation significantly mediated the prediction of reduced anxiety- and depression-related emotional eating over 6 months by improvements in tension and depression, respectively. The emotional eating reductions were significantly associated with weight loss over both 6 and 24 months. Increased physical activity was significantly associated with reduced tension and depression. We also found that the relationship between changes in physical activity and tension was significantly mediated by a change in exercise-related self-efficacy. Increased exercise self-regulation significantly predicted improved eating regulation, with eating-related self-efficacy change being a significant mediator. Our findings suggest an array of psychosocial targets for behavioral weight-management treatments that have large-scale applications.