Objective To improve understanding of directionality in the dynamic relationships among psychosocial predictors of behavioral changes associated with weight loss. Methods In women with obesity participating in a new behavioral weight-loss treatment that emphasizes physical activity (n = 53; body mass index = 34.7 ± 3.3 kg/m2), mediation and moderated-mediation models were fit to assess directionality in the self-efficacy–self-regulation change relationship and additional effects of mood change and its basis on fruit/vegetable intake and physical activity behaviors through month 6 and from months 6 to 24. Results Self-regulation was a stronger predictor of change in self-efficacy than vice versa. Mood change did not moderate the relationships significantly between changes in self-efficacy and/or self-regulation, and weight loss behavior. Emotional eating significantly changed mediated relationships between changes in mood and fruit/vegetable intake through month 6 (95% confidence interval, –0.05 to 0.00). Conclusions and Implications Findings clarified relationships of self-efficacy, self-regulation, and mood in the prediction of weight loss behaviors, and informed behavioral treatments for improved outcomes.