Cyberbullying has emerged as a pervasive problem among high school students, with potentially severe consequences for their mental well-being. This study aimed to investigate the prevalence, risk factors, and associations of cyberbullying with stress and mental well-being among high school students in Zagazig, Egypt. A cross-sectional study was conducted among 562 high school students using a random sampling technique. The data were collected using a self-administered questionnaire that included the Cyberbullying Scale, Perceived Stress Scale (PSS-10), and General Health Questionnaire (GHQ-12). Descriptive statistics, independent samples t-tests, multiple regression, mediation, and logistic regression analyses were employed for data analysis. The prevalence of cyberbullying victimization was 38.3%, with 20.6% exposed to two or three cyberbullying behaviors and 4.1% exposed to four or more. Female students, those under 18 years old, those with lower educational achievement, and those with higher daily internet use were more likely to experience cyberbullying. Cyberbullied students reported significantly higher levels of perceived stress and poorer mental well-being compared to non-cyberbullied students. Perceived stress likely mediated the relationship between cyberbullying victimization and general psychological health. Cyberbullying is a significant problem among high school students in Zagazig, Egypt, with detrimental effects on their stress levels and mental well-being. Targeted interventions and prevention strategies are needed to address cyberbullying and promote the well-being of adolescents in the digital age.