Background: Amputation confers disabilities upon patients and is associated with substantial cardiovascular and metabolic morbidity and mortality. We aimed to compare the incidence of end-stage kidney disease (ESKD) between individuals with amputation and the general population. Methods: A population-based retrospective cohort study was performed using the Nationwide Health Insurance Service database for the period between 2010 and 2018. A total of 24,925 individuals with amputation were included with a ratio of 1:3 age- and sex-matched controls. A Cox proportional hazards regression analysis was used to calculate the risk of ESKD among amputees. Results: During a mean follow-up period of 4.3 years, there were 40 incident ESKD cases (0.4 per 1000 person-years) among individuals with amputation. Individuals with amputation showed a higher risk of ESKD (adjusted HR [aHR] of 1.75, 95% confidence interval [CI] of 1.20–2.54) compared with matched controls. The risk was further increased in those with mild disability (aHR of 1.41, 95% CI of 0.51–3.87) and severe disability (aHR of 8.22, 95% CI of 2.99–22.61). When considering the levels of amputation, the association was apparently more prominent in proximal than distal amputation, in particular for proximal upper limb amputation (aHR of 17.90, 95% CI of 4.37–73.40). Conclusions: Individuals with amputation were at a significantly greater risk of ESKD than the general population, particularly subjects with severe disability and proximal amputation. Our data suggest that amputations should be added to the list of risk factors for the development of chronic kidney disease.