Limited evidence exists on the effects of weight loss on chronic disease risk and patientreported outcomes in breast cancer survivors. Breast cancer survivors (stage I-III; body mass index 25–45 kg/m2) were randomized to a 12-month, remotely delivered (22 telephone calls, mailed material, optional text messages) weight loss (diet and physical activity) intervention (n = 79) or usual care (n = 80). Weight loss (primary outcome), body composition, metabolic syndrome risk score and components, quality of life, fatigue, musculoskeletal pain, menopausal symptoms, fear of recurrence, and body image were assessed at baseline, 6 months, 12 months (primary endpoint), and 18 months. Participants were 55 ± 9 years and 10.7 ± 5.0 months post-diagnosis; retention was 81.8% (12 months) and 80.5% (18 months). At 12-months, intervention participants had significantly greater improvements in weight (−4.5% [95%CI: −6.5,−2.5]; p < 0.001), fat mass (−3.3 kg [−4.8,−1.9]; p < 0.001), metabolic syndrome risk score (−0.19 [−0.32,−0.05]; p = 0.006), waist circumference (−3.2 cm [−5.5,−0.9]; p = 0.007), fasting plasma glucose (−0.23 mmol/L [−0.44,−0.02]; p = 0.032), physical quality of life (2.7 [0.7,4.6]; p = 0.007; Cohen’s effect size (d) = 0.40), musculoskeletal pain (−0.5 [−0.8,−0.2]; p = 0.003; d = 0.49), and body image (−0.2 [−0.4,−0.0]; p = 0.030; d = 0.31) than usual care. At 18 months, effects on weight, adiposity, and metabolic syndrome risk scores were sustained; however, significant reductions in lean mass were observed (−1.1 kg [−1.7,−0.4]; p < 0.001). This intervention led to sustained improvements in adiposity and metabolic syndrome risk.