Background <p>Early-life undernutrition, particularly during critical developmental periods, may have lasting impacts on non-communicable diseases (NCDs) in adulthood. The Chinese Great Famine (1959–1961) provides a unique opportunity to evaluate these effects in a large-scale population study. To investigate the impact of early-life undernutrition on adult mortality due to NCDs in individuals exposed to the Chinese Great Famine.</p> Methods <p>We analyzed data from a medical insurance database in Hua County, China, including 15,088 individuals born during the famine (1959–1961) and 49,924 individuals deemed unexposed because they were born after the famine (1962–1964), with follow-up from 2012 to 2023. Multivariable Cox regression and competing risks regression were used to assess the association between early-life undernutrition and mortality.</p> Results <p>Early-life undernutrition was associated with increased risks of all-cause mortality (HR_adjusted = 1.49, 95% CI 1.37–1.62), cancer mortality (HR_adjusted = 1.41, 95% CI 1.22–1.64), cardiovascular and cerebrovascular diseases mortality (HR_adjusted = 1.51, 95% CI 1.34–1.71), and chronic obstructive pulmonary disease mortality (HR_adjusted = 4.37, 95% CI 2.51–7.61). Subgroup analysis revealed that the exposed group had a higher risk of death from lung, esophageal, gastric, hepato-biliary, and pancreatic cancers, cerebrovascular disease and cardiovascular disease.</p> Conclusions <p>This study demonstrates the long-term adverse effects of early-life undernutrition on NCD mortality in adulthood, underscoring the importance of nutritional interventions during critical developmental periods to reduce the burden of NCDs.</p> <i>Clinical trial registration</i> <p>Endoscopic Screening for Esophageal Cancer in China (ESECC) randomized controlled trial (Clinical trial: NCT01688908).</p>