Abstract Background: Coronary heart disease (CHD) remains the leading cause of morbidity and mortality in the United States and worldwide. Although body mass index (BMI) is widely used to measure obesity, it fails to account for fat distribution. The Weight-Adjusted Waist Index (WWI), that is, waist circumference standardized by weight, has emerged as a superior indicator of central adiposity and cardiometabolic risk. Smoking, a major modifiable risk factor for CHD, also influences body fat distribution and may modify the relationship between adiposity and cardiovascular outcomes. This study examined the association between WWI and CHD among U.S. adults and assessed whether smoking status moderates this relationship. Methods: A cross-sectional analytic study was conducted using data from 5,175 adults aged ≥20 years from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Coronary heart disease was defined by physician diagnosis or self-reported history of CHD, angina, or heart attack. WWI was computed as waist circumference (cm) divided by the square root of body weight (kg). Survey-weighted logistic regression models assessed the independent and interactive effects of WWI and smoking status (never, former, current) on CHD, adjusting for demographic and cardiometabolic covariates. Model discrimination was evaluated using ROC analysis. Results: Participants with CHD were significantly older (p < 0.0001), predominantly male (64.3%), and more likely to be hypertensive (75.1%), diabetic (15.9%), or dyslipidemia (67.3%). Mean WWI was higher among CHD participants (11.56 ± 0.08, p < 0.0001). Current smokers had over twice the odds of CHD compared to never smokers (OR = 2.26, p = 0.0047). While WWI was positively associated with CHD risk, the interaction between WWI and smoking was not statistically significant. ROC analysis demonstrated that WWI (AUC = 0.685) was a stronger discriminator of CHD than BMI (AUC = 0.537, p < 0.0001). Conclusion: WWI is a superior anthropometric indicator of CHD risk compared with BMI. Although smoking independently increased CHD risk, it did not significantly modify the WWI–CHD association. Integrating central adiposity assessment with smoking cessation strategies may enhance cardiovascular disease prevention and risk stratification in U.S. adults.