Behavior change interventions are effective to the extent that they affect appropriately-measured outcomes, especially in experimental controlled trials. The primary goal of this study was to analyze the impact of a 1-year weight management intervention based on self-determination theory (SDT) on theory-based psychosocial mediators, physical activity/exercise, and body weight and composition. Participants were 239 women (37.6 ± 7.1 years; 31.5 ± 4.1 kg/m2) who received either an intervention focused on promoting autonomous forms of exercise regulation and intrinsic motivation, or a general health education program (controls). At 12 months, the intervention group showed increased weight loss (−7.29%,) and higher levels of physical activity/exercise (+138 ± 26 min/day of moderate plus vigorous exercise; +2,049 ± 571 steps/day), compared to controls (P < 0.001). Main intervention targets such as more autonomous self-regulation (for treatment and for exercise) and a more autonomous perceived treatment climate revealed large effect sizes (between 0.80 and .96), favoring intervention (P < 0.001). Results suggest that interventions grounded in SDT can be successfully implemented in the context of weight management, enhancing the internalization of more autonomous forms of behavioral regulation, and facilitating exercise adherence, while producing clinically-significant weight reduction, when compared to a control condition. Findings are fully consistent with previous studies conducted within this theoretical framework in other areas of health behavior change.