Introduction Oral lesions are frequent complications of Human Immunodeficiency Virus (HIV) infection, particularly among individuals with advanced immunosuppression. These lesions reduce quality of life and increase vulnerability to secondary infections. This study assessed knowledge, risk factors, and healthcare-seeking behavior related to oral lesions among HIV enrollees in Osun State, Nigeria.Methodology A descriptive cross-sectional study was conducted among 180 HIV-positive adults attending Antiretroviral Therapy (ART) clinics, selected using multistage sampling. A structured, interviewer-administered questionnaire—validated by oral health and HIV experts was used to collect data on socio-demographics, knowledge of oral lesions, risk factors (e.g., smoking, poor oral hygiene, ART adherence), and healthcare-seeking practices. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 20. Descriptive statistics summarized participant characteristics. Chi-square tests assessed associations between variables (p < 0.05).Results Participants were mostly male (51.7%) and Yoruba (74.4%). Only 56.1% had good knowledge of oral lesions. Common risk factors included poor oral hygiene (56.1%), alcohol use (31.7%), and ART non-adherence. Healthcare-seeking within two weeks of symptoms was low (26.7%). Religion, education, and occupation were significantly associated with care-seeking. Poor oral hygiene and low CD4 counts were significant predictors of oral lesions.Conclusion Knowledge and prompt care-seeking for oral lesions remain inadequate among HIV enrollees. Integrating oral health education, routine screening, and dental care into HIV treatment services is essential to improve outcomes in this population.