Abstract Background The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) represents a novel composite lipid marker for atherosclerosis and cardiovascular disease (CVD). Nevertheless, the correlation between NHHR and mortality in the non-diabetic population remains indistinct. Methods This study included 20,774 non-diabetic individuals from the 1999–2018 National Health and Nutrition Examination Survey (NHANES). We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR, its combination with obesity indicators, and all-cause and CVD mortality. Results During a mean follow-up period of 62 months, a total of 897 participant deaths were recorded, of which 155 were attributed to cardiovascular causes. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for CVD mortality. The analysis of threshold efects revealed that the infection points for NHHR and all-cause and CVD mortality were 2.65 and 2.07, respectively. The cubic spline revealed a nonlinear correlation was observed between NHHR-BMI, NHHR-WC and NHHR-WHtR and all-cause and CVD mortality. Conclusion NHHR and its combination with obesity indicators can be a meaningful predictor of all-cause mortality and CVD mortality in non-diabetic individuals.