Currently, the debate surrounding the regulation of e-cigarettes focuses mainly on the size of e-cigarettes’ potentially beneficial effects (i.e., adult cessation) versus their unwarranted effects (i.e., initiation among tobacco-naïve adolescents). Therefore, we investigated the relative scale of e-cigarette use transitions in the United States. We reported cross-sectional weighted prevalence estimates of past-month e-cigarette use by ever cigarette use from Waves 1–4 of the Population Assessment of Tobacco and Health study (2013–2018) among youth (12–17 years) and adults (≥ 18 years). We also examined past-month e-cigarette mono and dual transitions related to cigarette smoking and reported the longitudinal weighted prevalence across waves. Among youth new e-cigarette users, the proportion of never-cigarette smokers increased from 24.1 in Wave 1 (n = 418) to 51.4% in Wave 4 (n = 310) (p < 0.0001 for trend). Of youth past-month e-cigarette mono-users in Wave 1 (n = 151), 15.2% transitioned to cigarette mono-use and 8.2% dual-use at Wave 2 or 3 or 4, compared to 60.2% no tobacco use and 16.4% e-cigarette mono-use. Among young adult past-month dual-users (18–24 years; n = 684), 22.6% transitioned to no tobacco use, 60.1% continued cigarette use, 11.4% dual use, and 5.9% e-cigarette mono-use. Among adult dual-users ≥ 25 years old (n = 1560), 13.6% transitioned to no tobacco use, 71.3% cigarette mono-use, 9.0% dual-use, and 6.1% e-cigarette mono-use. Transition to cigarette mono-use and continued dual-use were common among adult past-month e-cigarette users, while e-cigarette initiation was common among youth never-cigarette smokers. These findings contrast with data from other countries showing limited evidence of e-cigarette initiation among youth never cigarette smokers. Both e-cigarette and cigarette use should be addressed in youth and adults, given the potential for dual use in both populations.