Background: Behavioral obesity treatments remain primarily based on nutrition and exercise education, with their minimal effects persisting over many decades. Research suggests benefits of an alternate focus on psychosocial factors. Aim: To evaluate treatment aspects that foster accumulated impacts on weight-loss behaviors via interactions between supported changes in self-efficacy and self-regulation. Methods: Women with obesity participating in a theory-based behavioral weight-loss treatment targeting self-regulation and self-efficacy to foster increases in fruit/vegetable consumption and physical activity (N = 95) were assessed at intervals from baseline through 12 months. Results: The treatment was associated with significant improvements in the tested psychosocial and behavioral variables. Hypothesized paths from baseline self-efficacy → 3-month increases in self-regulation → 6-month increases in self-efficacy → 12-month increases in self-regulation → 12-month behavioral changes were significant in predicting both fruit/vegetable intake and physical activity increases. Most of the variance in weight loss was explained through physical activity change. Conclusion: Targeting self-regulation, self-efficacy, and their over-time interactions enhances behavioral weight-loss treatment outcomes.