E-cigarette use is increasing among adolescents, despite potential harms. Social media messages are a promising way to educate youth about e-cigarettes, yet little is known about what message topics and formats will have beneficial impacts for message reception, reach, e-cigarette knowledge, and beliefs about harms. A national convenience sample of adolescents (n = 928, aged 15–18 years) in high school was recruited for an online experiment. In October 2019, participants were randomized to view one of three social media formats (visual based, quiz, and text only) or a no-message control. Participants in format conditions viewed six unique topics in a random order. Outcomes were e-cigarette knowledge and beliefs. Message reactions and sharing preferences were also assessed among youth who saw social media messages. Social media messages led to greater knowledge (Cohen's f = .19; p < .001) and beliefs (f = .16; p < .001) about harms of e-cigarettes compared with the control, regardless of format. Almost four in five adolescents (79%) reported they would share the social media messages, most likely in person (49%) and with friends (52%). Message topics for missing out because of lung damage, having uncontrolled moods, and ingesting specific harmful chemicals elicited higher intended message reactions. Social media messages can educate about e-cigarette harms. Social media campaigns are a promising e-cigarette education strategy to reach youth, directly and potentially through peer-to-peer sharing.