Using a 12-item questionnaire, we assessed knowledge, attitudes, and practice (KAP) toward epilepsy and identified determinants of inappropriate attitudes toward people with epilepsy (PWE) among 910 randomly selected secondary school students in Batibo (Cameroon). Ninety-five percent of the students had heard or read about epilepsy, 73.3% knew an epileptic, and 76.4% had witnessed a seizure. Those who would offer equal employment opportunities to PWE, refuse to associate with, or refuse to marry PWE represented 58.6%, 25.4%, and 64.2%, respectively. Negative attitudes appeared to be reinforced by beliefs that epilepsy is hereditary (25.7%), contagious (49.9%), or a kind of insanity (38%). Acquaintance with PWE tended to improve the misconception that epilepsy is contagious (p < 0.001), and to reinforce the view that it is a form of insanity (p < 0.01). A successful epilepsy education program must account for local beliefs, and secondary school students may constitute a good channel for community education.