Weight gain after breast cancer diagnosis is associated with adverse health outcomes. Yet, few studies have characterized post-diagnosis weight change in the modern treatment era or populations most at risk for weight changes. Among women diagnosed with stages I–III breast cancer in the Smilow Care Network (2013–2019; N = 5441), we abstracted demographic and clinical characteristics from electronic health records and survival data from tumor registries. We assessed if baseline characteristics modified weight trajectories with nonlinear multilevel mixed-effect models. We evaluated body mass index (BMI) at diagnosis and weight change 1-year post-diagnosis in relation to all-cause and breast cancer-specific mortality with Cox proportional hazard models. Women had 34.4 ± 25.5 weight measurements over 3.2 ± 1.8 years of follow-up. Weight gain was associated with ER/PR−, HER2+ tumors, BMI ≤ 18.5 kg/m2, and age ≤ 45 years (+4.90 kg (standard error [SE] = 0.59), +3.24 kg (SE = 0.34), and +1.75 kg (SE = 0.10), respectively). Weight loss was associated with BMI ≥ 35 kg/m2 and age ≥ 70 years (−4.50 kg (SE = 0.08) and −4.34 kg (SE = 0.08), respectively). Large weight loss (≥10%), moderate weight loss (5–10%), and moderate weight gain (5–10%) 1-year after diagnosis were associated with higher all-cause mortality (hazard ratio [HR] = 2.93, 95% confidence interval [CI] = 2.28–3.75, HR = 1.32, 95% CI = 1.02–1.70 and HR = 1.39, 95% CI = 1.04–1.85, respectively). BMI ≥ 35 kg/m2 or BMI ≤ 18.5 kg/m2 at diagnosis were also associated with higher all-cause mortality. Weight change after a breast cancer diagnosis differed by demographic and clinical characteristics highlighting subgroups at-risk for weight change during a 5-year period post-diagnosis. Monitoring and interventions for weight management early in clinical care are important.