Lassa fever is an extremely virulent and highly infectious disease endemic in West Africa, including Nigeria. This study aimed to assess the knowledge, attitudes, and preventive practices against Lassa fever among adult residents of Akure South Local Government in Ondo State, Nigeria. A cross-sectional study design was utilized, with data collected from adults in the LGA during a recent outbreak. The study involved systematic random sampling of approximately 300 adults, with data collected via pretested, interviewer-administered questionnaires. The study employed a multi-stage sampling technique and used a pretested interviewer-administered questionnaire. Data were analyzed using frequency distribution tables, simple percentages, and bar charts. The findings indicated that only 33.6% of respondents had good knowledge of Lassa fever, while 54.3% practiced good food and environmental hygiene. Most respondents were female, highly literate, and predominantly Yoruba. Despite high awareness, misconceptions about Lassa fever's origin and nature persisted, with many believing it was discovered in Congo or considering it a chronic disease. Effective prevention practices such as proper food storage were acknowledged, aligning with recommendations to avoid contact with Mastomys rodents and maintain cleanliness to prevent rodent infestations. The study concluded that there is a need for improved risk communication, ongoing sensitization, and specific educational campaigns to enhance understanding and preventive behaviors regarding Lassa fever. Further research is recommended to expand these findings across Ondo State and compare risk perceptions in affected and unaffected communities.