Purpose: Although exercise is typically included in behavioral weight-loss programs, the amount associated with meaningful short- to long-term weight reduction required investigation. Indirect paths between exercise-associated psychological changes and weight loss might be more relevant than the direct effect of exercise on energy expenditure-related weight loss in deconditioned/obese individuals. Method: Sedentary women with obesity (N = 97; M age = 47.2 years) participated in a year-long cognitive-behavioral weight-loss treatment that emphasized building self-regulatory skills to maintain exercise in advance of transferring those skills to controlled eating. Results: There was a significant increase in exercise (metabolic equivalents/week or leisure score index; LSI), and significant improvements in mood, self-regulation for exercise, and self-regulation for eating from baseline to Months 6, 12, and 24. There were 5.9%, 5.8%, and 5.8% reductions in weight, respectively. Completion of 15-20 LSI did not significantly differ from greater amounts on associated weight losses except for the rare occurrence of ≥ 30 LSI over the full 24-month study period. There were significant bivariate relationships between completion of ≥ 15 LSI and weight loss over 6, 12, and 24 months. Within serial mediation analyses assessing changes from baseline-Months 6 and 24, there were significant indirect paths from ≥ 15 LSI→self-regulation for exercise→self-regulation for eating→weight loss, and ≥ 15 LSI→negative mood→self-regulation for exercise→self-regulation for eating→weight loss. Those paths were not significant when baseline-Month 12 changes were entered. Conclusion: Findings suggested the value of even manageable exercise amounts because of their association with psychosocial correlates of weight loss, and informed behavioral obesity treatments.