Cigarette smoking contributes to numerous diseases and is one of the leading causes of death in the United States. Smoking behaviors vary widely across race/ethnicity, but it is not clear why. Here, we examine the contribution of genetic ancestry to variation in two smoking-related traits in 43,485 individuals from four race/ethnicity groups (non-Hispanic white, Hispanic/Latino, East Asian, and African American) from a single U.S. healthcare plan. Smoking prevalence was the lowest among East Asians (22.7%) and the highest among non-Hispanic whites (38.5%). We observed significant associations between genetic ancestry and smoking-related traits. Within East Asians, we observed higher smoking prevalence with greater European (versus Asian) ancestry (P = 9.95 × 10-12). Within Hispanic/Latinos, higher cigarettes per day (CPD) was associated with greater European ancestry (P = 3.34 × 10-25). Within non-Hispanic whites, the lowest number of CPD was observed for individuals of southeastern European ancestry (P = 9.06 × 10-5). These associations remained after considering known smoking-associated loci, education, socioeconomic factors, and marital status. Our findings support the role of genetic ancestry and socioeconomic factors in cigarette smoking behaviors in non-Hispanic whites, Hispanic/Latinos, and East Asians.