Adolescents' susceptibility to pro-tobacco marketing advertisements puts them at risk for initiating and continued use of tobacco. The objective of this study was to quantify the cross-sectional association between tobacco ad exposure and tobacco use susceptibility (e.g., curiosity about tobacco products, willingness, and future intention to try tobacco products) among tobacco-naive adolescents. Data came from Wave 4 of the Population Assessment of Tobacco and Health (PATH) study, a nationally-representative sample of US adolescents ages 12–17. We used logistic regression to examine (1) characteristics associated with tobacco ad exposure; (2) associations between tobacco ad exposures (by product type/venue) and tobacco use susceptibility (among tobacco-naive adolescents only). The results suggested that higher household income, living with tobacco user(s), substance use history, and mental health problem(s) were associated with increased odds of tobacco marketing exposure. Among tobacco naïve adolescents (N = 9455), tobacco ads exposure was positively associated with tobacco use susceptibility, compared with the non-exposure group. Seeing cigarettes/other non-ENDS tobacco products only was associated with a 1.64 increase in odds being susceptible to tobacco use; tobacco ads exposure via website and/or social media sites only (cigarette/other non-ENDS tobacco, AOR: 1.87, 95%CI: 1.25–2.81; ENDS, AOR: 2.25, 95%CI: 1.43–3.55) was associated with higher odds of tobacco use susceptibility, compared to the non-exposure group. With rapidly increasing rates of ENDS use in adolescents, it is crucial that advertisements promoting the initiation and continued use of ENDS are strictly regulated, especially among advertisements that are online and on social media sites.