Throughout the last decade, adolescent use of electronic nicotine delivery systems (ENDS) has increased significantly. The products are not subject to nearly the same regulations or advertising restrictions as traditional cigarettes. The purpose of this research was to investigate the association between exposure to several channels of e-cigarette advertisement and adolescent use of the products. Secondary data were obtained from the 2019 National Youth Tobacco Survey (N = 18000), which gathered information from students in grades 6 through 12. Four channels of e-cigarette advertisements were identified (Internet, print, retail, and TV) and exposure was measured using five response options: never, rarely, sometimes, most of the time, and always. Separate logistic regression models were employed to assess the relationship between e-cigarette advertising and ENDS use, adjusting for age, gender, school level, ethnicity, and race. A subgroup analysis of age was included to assess how use of ENDS by advertisement exposure may differ between three distinct age ranges (11–13, 14–15, and 16–18). The findings indicate a significant association between exposure to e-cigarette advertisements and ENDS use by adolescents in the United States. Among all age groups, print advertisements are less correlated to ENDS use than the other advertisement channels. Findings suggest that early- adolescents (11–13) have the highest odds of ENDS use, particularly in relation to Internet and retail advertisement channels. Future longitudinal studies are needed to investigate whether a causal relationship between advertising and ENDS use exists. Given the harmful health impacts linked to nicotine use and the unknown impacts of ENDS, strategic prevention and control measures are needed to protect vulnerable populations such as adolescents.