Cardiovascular and renal conditions have both shared and distinct determinants. In this study, we applied unsupervised clustering to multiple rounds of the National Health and Nutrition Examination Survey from 1988 to 2018, and identified 10 cardiometabolic and renal phenotypes. These included a ‘low risk’ phenotype; two groups with average risk factor levels but different heights; one group with low body-mass index and high levels of high-density lipoprotein cholesterol; five phenotypes with high levels of one or two related risk factors (‘high heart rate’, ‘high cholesterol’, ‘high blood pressure’, ‘severe obesity’ and ‘severe hyperglycemia’); and one phenotype with low diastolic blood pressure (DBP) and low estimated glomerular filtration rate (eGFR). Prevalence of the ‘high blood pressure’ and ‘high cholesterol’ phenotypes decreased over time, contrasted by a rise in the ‘severe obesity’ and ‘low DBP, low eGFR’ phenotypes. The cardiometabolic and renal traits of the US population have shifted from phenotypes with high blood pressure and cholesterol toward poor kidney function, hyperglycemia and severe obesity.