Hypertension is a prevalent chronic non-communicable disease associated with cardiovascular issues, strokes, kidney disorders, and depression. Most hypertensive patients have dyslipidemia and metabolic abnormalities. The non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) is a novel index that more accurately assesses the risk of atherosclerotic cardiovascular diseases and metabolic issues like insulin resistance. The association between NHHR and hypertension prevalence is still unclear. The study aims to examine the link between NHHR and hypertension prevalence in American adults. N10,410 adults from the National Health and Nutrition Examination Survey (NHANES) (2005-2016) were included in this cross-sectional analysis. Multivariable logistic regression constructed to analyze the relationship between NHHR and hypertension, with additional analyses including restricted cubic spline regression (RCS), threshold and saturation effect analyses, effect point calculations, subgroup analyses, and sensitivity analyses. Machine learning methods combined with the Boruta algorithm were employed to identify key predictors of hypertension risk. Of the 10,410 participants, 48% were male, with a hypertension prevalence of 37.03%. NHHR was higher in hypertensive patients compared to non-hypertensive individuals (2.74 vs 2.90, P < .001). In models that were completely confounded with factors including general demographic data, BMI, smoking status, alcohol consumption, diabetes, total cholesterol, history of coronary heart disease, LDL, and dietary cholesterol, NHHR showed a significant positive correlation with hypertension prevalence. RCS regression indicated a non-linear relationship, with a saturation effect point at 3.058. Subgroup analyses showed significant interactions by race and education level (P < .05). Machine learning models demonstrated AUCs > 0.8, affirming the importance of NHHR in predicting hypertension. NHHR levels are significantly elevated in hypertensive individuals compared to non-hypertensive adults in the U.S. Furthermore, a non-linear positive correlation exists between NHHR and hypertension risk, suggesting its potential as a predictive biomarker for early hypertension prevention.Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.