Objectives: Life-course models have been infrequently applied to physical function. We sought to examine the effects of the cumulative burden of cardiovascular risk factors (CVRFs) from childhood on physical function in midlife. Methods: This longitudinal study consisted of 718 participants (aged 37 to 56 years at follow-up) who were examined for CVRFs at least four times during childhood and at least twice in adulthood, with 39 years of follow-up. We assessed physical function in 2013-2016 with the Short Physical Performance Battery (SPPB), 6-minute walking test (6MWT), and handgrip strength. The area under the growth curve (AUC) was used as a measure of cumulative exposure to CVRFs during childhood. Results: AUC of HDL-cholesterol levels in childhood were positively associated with SPPB score. AUC levels of body mass index (BMI) and triglycerides (TG) were inversely associated with 6MWT. Higher AUC levels of systolic/diastolic blood pressure (BP) predicted poorer hand grip strength. The number of childhood CVRFs in the top quartile, including AUC levels of BMI and TG, were inversely associated with 6MWT and remained significant after adjustment for the adulthood CVRFs. Conclusion: Cumulative burden of CVRFs from childhood were associated with worse physical function in midlife independent of adulthood CVRFs.