Abstract Background and Aims Estimated glomerular filtration rate (eGFR), a significant measurement of chronic kidney disease (CKD), is associated with adverse health outcomes in the general population but whether its utility differs by race and genetic risk remains unclear. The current study aims to investigate the performance of CKD staging and risk prediction in cardiovascular disease and mortality based on five eGFR measures among people of different ethnic groups and genetic background. Method In this prospective cohort study, we included 431,126 participants from the UK Biobank, deriving hazard ratios and 95% confidence intervals from multivariable adjusted Cox proportional hazards models. C statistic and net reclassification improvement (NRI) were utilized for comparing the predictive benefit of eGFR measures when added to the traditional cardiovascular risk factors. Results Over a median of 13.4 (IQR 12.7-14.9) years of follow-up, 27,757 (6.4%) participants died from any cause, of which 3272 (0.8%) died primarily from CVD. 39,522 (9.2%) incident composite CVD hospitalization and 911 (0.2%) ESRD occurred. Two new eGFR equations refitted without race provided lower estimates in Black population but higher in other ethnic backgrounds than the corresponding old ones. The relative risk of adverse outcomes was generally greater in Blacks and participants with low genetic susceptibility to impaired kidney function. The superiority of cystatin C-based eGFR measures in risk prediction did not differ by race and genetic risk. Conclusion Eliminating the use of racial categories in eGFR calculation help enhance the access to specialist care and intervention at the early stage of CKD for Black population. Cystatin C-based eGFR measures can be extensively used in risk assessment in clinical practice.