High weight gain in pregnancy is associated with greater postpartum weight retention; yet the long-term implications remain unknown. Our objective was to assess whether pregnancy weight gain was associated with women’s long-term mortality over 50 years later. The Collaborative Perinatal Project (CPP) Mortality Linkage Study linked maternal participants in the CPP, a prospective pregnancy cohort (1959-1965), to the National Death Index and Social Security Death Master File for vital status through 2016. In this diverse cohort of 46,042 U.S. women with a median follow-up of 52 years ((interquartile range 45-54), 38.9% of women died. Median (interquartile range) total gestational weight change was 9.5 kg (6.4-12.2); 2.5% lost weight during pregnancy. Pregnancy weight change had a U-shaped relationship with long-term mortality. Compared to women with average weight gain (quintile 3), women with weight loss or lowest weight gain (quintile 1), and women with highest weight gain (quintile 5), had a significant 7% and 9% increased mortality risk, respectively. Compared to average weight gain, HRs (95% confidence intervals) for the top four causes of death from cancer, cardiovascular disease, respiratory disease, and diabetes for the first quintile were 1.20 (0.99-1.46), 1.05 (0.96-1.15), 1.14 (0.96-1.37), and 0.92 (0.72-1.17), respectively; HRs for the fifth quintile were 1.19 (0.98-1.45), 1.14 (1.03-1.27), 0.95 (0.78-1.14), and 1.52 (1.20-1.92) respectively. This study’s novel findings reinforce the importance of healthy pregnancy weight gain beyond the pregnancy window to women’s long-term mortality risk, particularly from chronic diseases.