There is little recent information about the prevalence of symptomatology of mental health disorders in representative population samples in Mexico. To determine the prevalence of mental health symptoms in Mexico and its comorbidity with tobacco, alcohol, and drug use disorder (SUD), we used the 2016–17 National Survey of Drug, Alcohol, and Tobacco Use (Encuesta Nacional de Consumo de Drogas, Alcohol y Tabaco, ENCODAT 2016–2017). The data were collected from households using a cross-sectional, stratified, multistage design, with a confidence level of 90% and a response rate of 73.6%. The final sample included 56,877 completed interviews of individuals aged 12–65, with a subsample of 13,130 who answered the section on mental health. Symptoms of mania and hypomania (7.9%), depression (6.4%), and post-traumatic stress (5.7%) were the three main problems reported. Of this subsample, 56.7% reported using a legal or illegal drug without SUD, 5.4% reported SUD at one time on alcohol, 0.8% on tobacco, and 1.3% on medical or illegal drugs, 15.9% reported symptoms related to mental health, and 2.9% comorbidity. The prevalence found is consistent with those reported in previous studies, except for an increase in post-traumatic stress, which is consistent with the country’s increase in trauma.