<p>Sociopolitical stress associated with the policies and rhetoric coming from recent U.S. presidential administrations is of particular concern vis-à-vis Hispanic individuals, who have been disproportionately targeted for detention and deportation. Such stress may be associated with symptoms of depression and anxiety, and ultimately with tobacco use. However, there is a paucity of research examining how sociopolitical stress is associated with mental health problems and substance use among Hispanic emerging adults. Accordingly, the present study was designed to examine the extent to which, within a sample of Mexican American college students, sociopolitical stress would be linked with tobacco use indirectly through symptoms of depression and anxiety. A cross-sectional sample of 997 Mexican American college students in Texas completed measures of sociopolitical stress, depressive symptoms, anxiety, and cigarette and e-cigarette use. More than 75% of participants agreed/strongly agreed with each of the sociopolitical stress items, suggesting high levels of sociopolitical stress within the sample. Structural equation models indicated that sociopolitical stress was associated directly with depressive symptoms (β = 0.16, <i>p</i> &lt; .001) and indirectly with both cigarette (<i>b</i> = 0.01, 95% CI = 0.002, 0.015) and e-cigarette (<i>b</i> = 0.02, 95% CI = 0.005, 0.033) use and sociopolitical stress was associated directly with anxiety (β = 0.16, <i>p</i> &lt; .001) and indirectly with both cigarette (<i>b</i> = 0.01, 95% CI = 0.001, 0.014) and e-cigarette (β = 0.02, 95% CI = 0.008, 0.037) use. Intervention and policy work is needed to offset the associations of sociopolitical stress associated with recent U.S. administrations vis-à-vis mental health symptoms and tobacco use among Hispanic populations, including college students.</p>