Few studies have been conducted that have examined the long-term effect of different doses of physical activity (PA) on weight change in overweight adults without a prescribed reduction in energy intake. This study examined the effect of different prescribed doses of PA on weight change, body composition, fitness, and PA in overweight adults. Two hundred seventy-eight overweight adults (BMI: 25.0-29.9 kg/m²; age: 18-55 years) with no contraindications to PA were randomized to one of three intervention groups for a period of 18 months. MOD-PA was prescribed 150 min/week and HIGH-PA 300 min/week of PA. Self-help group (SELF) was provided a self-help intervention to increase PA. There was no recommendation to reduce energy intake. MOD-PA and HIGH-PA were delivered in a combination of in-person and telephone contacts across 18 months. 18-month percent weight change was -0.7 ± 4.6% in SELF, -0.9 ± 4.7% in MOD-PA, and -1.2 ± 5.6% in HIGH-PA. Subjects were retrospectively grouped as remaining within ±3% of baseline weight (WT-STABLE), losing >3% of baseline weight (WT-LOSS), or gaining >3% of baseline weight (WT-GAIN) for secondary analyses. 18-month weight change was 0.0 ± 1.3% for WT-STABLE, +5.4 ± 2.6% for WT-GAIN, and -7.4 ± 3.6% for WT-LOSS. 18-month change in PA was 78.2 ± 162.6 min/week for WT-STABLE, 74.7 ± 274.3 for WT-GAIN, and 161.9 ± 252.6 min/week for WT-LOSS. The weight change observed in WT-LOSS was a result of higher PA combined with improved scores on the Eating Behavior Inventory (EBI), reflecting the adoption of eating behaviors to facilitate weight loss. Strategies to facilitate the maintenance of these behaviors are needed to optimize weight control.