Background: Electronic cigarettes (e-cigarettes) are the most commonly used tobacco product among adolescents. We aimed to identify factors associated with e-cigarette susceptibility and curiosity among adolescents who are and are not susceptible to cigarette smoking. Method: Data were drawn from the 2018 U.S. National Youth Tobacco Survey. The study sample comprised 13,428 never cigarette or e-cigarette users. Four distinct weighted multivariable regression models were performed to assess associations between covariates and e-cigarette curiosity and susceptibility. Results: Among adolescents susceptible to smoking cigarettes, non-Hispanic (NH) Black participants were less likely to be susceptible to (adjusted odds ratio [aOR] = 0.42, 95% confidence interval [CI] [0.26, 0.67]) and curious about (aOR = 0.61, 95% CI [0.39, 0.95]) e-cigarettes than NH Whites. Among adolescents nonsusceptible to smoking cigarettes, Hispanics were more susceptible to (aOR = 1.33, 95% CI [1.04, 1.71]) and curious about (aOR = 1.29, 95% CI [1.02, 1.62]) e-cigarettes than NH Whites. Among adolescents (both susceptible and nonsusceptible to smoking cigarettes), being female, exposure to e-cigarette aerosol in public places, exposure to e-cigarette ads at point-of-sale, and having low perceived harm and addictiveness of e-cigarettes versus cigarettes were associated with having greater odds of susceptibility toward and curiosity about e-cigarette use. Conclusions: Future regulatory policies and tobacco control prevention campaigns should focus on increasing health awareness (e.g., potential harm and addictiveness) of e-cigarettes among adolescents and restrict marketing and the use of e-cigarettes in public places.