Behavioral (nonsurgical/nonpharmacologic) weight loss treatments have been overwhelmingly unsuccessful beyond the short term. Rather than incorporating accepted behavioral change theory, most have inadequately relied on providing exercise and nutrition information. Although adherence is a challenge, exercise has emerged as the most robust predictor of sustained weight reduction. However, exercise might be more associated with long-term weight loss through the relationship of its associated psychological changes with improved nutrition than through direct effects of energy expenditures, which are typically minimal in deconditioned individuals. To facilitate improved helping methods through a proposed theory-based causal chain model in which supported exercise predicts sustained weight loss through successive changes in exercise-related, then eating-related, self-regulation, self-efficacy, and mood. Segments of the model predict that 1) exercise and eating behaviors will be sequentially improved through increased self-regulatory skill use and self-efficacy and 2) exercise-induced mood improvements will foster greater self-regulation and reduced emotional eating. Short-term psychosocial changes can be leveraged to carry over to longer-term changes and maintained weight reductions. Suggested interventions emerging from the model and supporting research include using self-regulation to enable a habit of regular moderate exercise, facilitating a transfer of self-regulatory skills from an exercise to eating context, and leveraging mood improvements associated with manageable volumes of exercise to improve eating behaviors. The model presents an evidence-based explanation of the exercise-weight loss association through psychosocial mechanisms. It also informs the development of practical methods to facilitate sustainable reductions in weight and health risks in adults with obesity.