The influence of adiposity over life course on cancer risk remains poorly understood. We assessed trajectories of body shape from age 5 up to 60 using a group-based modeling approach among 73,581 women from the Nurses' Health Study and 32,632 men from the Health Professionals Follow-up Study. After a median of approximately 10 years of follow-up, we compared incidence of total and obesity-related cancers (cancers of the esophagus [adenocarcinoma only], colorectum, pancreas, breast [after menopause], endometrium, ovaries, prostate [advanced only], kidney, liver and gallbladder) between these trajectories. We identified five distinct trajectories of body shape: lean-stable, lean-moderate increase, lean-marked increase, medium-stable, and heavy-stable/increase. Compared with women in the lean-stable trajectory, those in the lean-marked increase and heavy-stable/increase trajectories had a higher cancer risk in the colorectum, esophagus, pancreas, kidney, and endometrium (relative risk [RR] ranged from 1.22 to 2.56). Early life adiposity was inversely while late life adiposity was positively associated with postmenopausal breast cancer risk. In men, increased body fatness at any life period was associated with a higher risk of esophageal adenocarcinoma and colorectal cancer (RR ranged from 1.23 to 3.01), and the heavy-stable/increase trajectory was associated with a higher risk of pancreatic cancer, but lower risk of advanced prostate cancer. The trajectory-cancer associations were generally stronger for non-smokers and women who did not use menopausal hormone therapy. In conclusion, trajectories of body shape throughout life were related to cancer risk with varied patterns by sex and organ, indicating a role for lifetime adiposity in carcinogenesis.