Abstract Background: Body mass index (BMI) is a known risk factor for renal cell cancer (RCC), but data are limited as to the effect of lifetime exposure to excess body weight. Methods: Using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 138,614, 527 incident RCCs), we identified several anthropometric measures to capture the lifetime BMI patterns: (i) BMI at specific ages; (ii) adulthood BMI trajectories; (iii) cumulative exposure to overweight/obesity denoted as weighted years of living overweight/obese (WYO); and (iv) weight change during each age span. We conducted multivariable Cox model to quantify the association between each anthropometric metric and incident RCC. Results: A higher BMI at ages 20 and 50 and at baseline was associated with a greater hazard of RCC. Compared with individuals who retained normal BMI throughout adulthood, we observed an increased hazard of RCC for BMI trajectory of progressing from normal BMI to overweight [HR, 1.49; 95% confidence interval (CI), 1.19–1.87], from normal BMI to obesity (HR, 2.22; 95% CI, 1.70–2.90), and from overweight to obesity (HR, 2.78; 95% CI, 1.81–4.27). Compared with individuals who were never overweight (WYO = 0), elevated HRs were observed among individuals who experienced low (HR, 1.31; 95% CI, 0.99–1.74), medium (HR, 1.57; 95% CI, 1.20–2.05), and high (HR, 2.10; 95% CI, 1.62–2.72) WYO tertile. Weight gain of ≥10 kg was associated with increased RCC incidence for each age span. Conclusions: Across the lifespan, being overweight/obese, weight gain, and higher cumulative exposure to excess weight were all associated with increased RCC risk. Impact: It is important to avoid weight gain and assess BMI from a life-course perspective to reduce RCC risk.