Kentucky ranks first in cancer incidence and second in cancer mortality rates, experiencing one of the heaviest cancer burdens in the United States. Further, the eastern Appalachian region of Kentucky faces severe cancer rates. Such disparities are due to health behaviors and social determinants of health, including environmental and community factors, economic instability, and low education attainment. More educated individuals with increased health literacy are less likely to engage in high-risk behaviors. Youth are especially vulnerable and are at risk of developing risky behaviors and habits; thus, youth cancer health education, as a preventative measure, is essential in reducing cancer prevalence. Previous research has shown that peer-led interventions have positive effects such as improving academic performance. Thus, this study aimed to implement a peer-led cancer education intervention in an Appalachian Kentucky K-12 school. Participants completed pre- and posttests measuring their cancer knowledge, as well as Likert-scale items and short answers regarding their perspectives. The intervention increased participants’ cancer knowledge in the experimental group (N = 24) compared to the control group (N = 32). The mean test score in the control group showed no significant change (t = 1.1071, p > 0.05), while the mean score in the experimental group increased from 58.5 to 65.3% (V = 55.5, p = 0.01). Answers to Likert-scale and short answer questions suggested that students perceived an increase in their cancer knowledge and thought that the use of peer teachers was a strength of the intervention. This study illustrates the effectiveness of a peer-led cancer education intervention that could reduce cancer health disparities in the long term.