This study investigates the prevalence of tobacco and alcohol uses and associated factors among 12 ethnic minorities in Vietnam in 2019. A cross-sectional survey was conducted among 5172 people aged ≥15 years. The prevalence of smoking and drinking was 19.7% and 29.9%, respectively, and significantly higher among men than women. These numbers were heterogeneous across ethnic minorities. Smoking prevalence was high among Ba Na (25.9%), Cham An Giang (22.3%), Khmer (23.5%), La Hu (26.3%), Ta Oi (30.7%), and Bru Van Kieu (29.6%) ethnicities whereas that of Gie Trieng and Mnong ethnicities was low (3.7% and 9.5%, respectively). Drinking prevalence ranged from 1.4% in Cham An Giang ethnicity to 68.6% in Ba Na ethnicity. A wide ethnic disparity on tobacco and alcohol use could be explained by the ethnic variation of lifestyles, social norms, and cultural features. Our findings suggest the need to develop ethnic-specific interventions to mitigate the smoking and drinking prevalence.