Introduction Previous research suggests the value of self-regulation for facilitating weight-loss behaviors. This study aimed to determine if improved mood has a facilitative effect on the self-regulation of healthy eating and exercise outputs associated within behavioral obesity treatments. Methods Data were from women with obesity (mean age = 47.1 ± 8.4 years; mean BMI = 35.0 ± 3.2 kg/m2) who previously participated in one of two community-based weight-loss treatment types over 6 months. One supported manual-based education on the need for healthy eating and increased exercise (n = 127). The other focused on self-regulation skills applied first to exercise, then eating behaviors (n = 107). Changes in exercise- and eating-related self-regulation, negative mood, exercise and eating behaviors, and weight were assessed. Results For both the psychological, exercise, and eating changes, effect sizes for within-group improvements were uniformly larger in the self-regulation group. Weight loss was 2.1% in the education group, and 6.3% in the self-regulation group. Based on 95% confidence intervals, changes in self-regulation over 3 months significantly mediated the prediction of changes in exercise, fruit/vegetable intake, and sweets consumption over 6 months by treatment type. Change over 3 months in mood significantly moderated (p-values ≤ 0.01) the above-indicated association of treatment type with self-regulation change. Mood score at month 3 was also a significant moderator (p-values < 0.05) in the models predicting eating changes. Increased fruit/vegetable intake significantly predicted reduced weight (p = 0.009), and reduced sweets, bread products, and dairy (p-values ≤ 0.01). Conclusion Findings clarified benefits for targeting self-regulation and mood within behavioral weight-loss treatments that go well-beyond typical processes of providing education on desirable behaviors.