Background: The study aimed to explore the association between early life and life-course exposure to social disadvantage and later life body mass index (BMI) accounting for genetic predisposition and maternal BMI. Methods: We studied participants of Helsinki Birth Cohort Study born in 1934–1944 (HBCS1934–1944, n = 1277) and Northern Finland Birth Cohorts born in 1966 and 1986 (NFBC1966, n = 5807, NFBC1986, n = 6717). Factor analysis produced scores of social disadvantage based on social and economic elements in early life and adulthood/over the life course, and was categorized as high, intermediate and low. BMI was measured at 62 years in HBCS1934–1944, at 46 years in NFBC1966 and at 16 years in NFBC1986. Multivariable linear regression analysis was used to explore associations between social disadvantages and BMI after adjustments for polygenic risk score for BMI (PRS BMI), maternal BMI and sex. Results: The association between exposure to high early social disadvantage and increased later life BMI persisted after adjustments (β = 0.79, 95% CI, 0.33, 1.25, p < 0.001) in NFBC1966. In NFBC1986 this association was attenuated by PRS BMI (p = 0.181), and in HBCS1934–1944 there was no association between high early social disadvantage and increased later life BMI (β 0.22, 95% CI –0.91,1.35, p = 0.700). In HBCS1934–1944 and NFBC1966, participants who had reduced their exposure to social disadvantage during the life-course had lower later life BMI than those who had increased their exposure (β − 1.34, [− 2.37,-0.31], p = 0.011; β − 0.46, [− 0.89,-0.03], p = 0.038, respectively). Conclusions: High social disadvantage in early life appears to be associated with higher BMI in later life. Reducing exposure to social disadvantage during the life-course may be a potential pathway for obesity reduction.