Background Oral potentially malignant disorders (OPMDs) represent a wide range of lesions with a substantial risk of malignant transformation. Betel quid chewing, prevalent in South Asia, is one of the main risk factors for OPMDs. Objective This study aimed to assess the prevalence of OPMDs in betel quid chewers and non-chewers and analyze their clinicopathological characteristics. Additionally, it aims to contribute to the existing literature on the correlation between betel quid use and the development of potentially malignant oral disorders. Methods A cross-sectional study involved 100 (50 betel quid chewers and 50 non chewers) participants from a tertiary care hospital in Peshawar and Lahore. Data were collected using structured clinical examinations, histopathological analyses, and a detailed questionnaire addressing chewing habits, lifestyle, and medical history. Statistical analysis was performed using logistic regression and chi-square tests. Results The prevalence of OPMDs was significantly higher in betel quid chewers (40%) compared to non-chewers (12%). Leukoplakia was the most common lesion in both groups. The odds of developing OPMDs were 5.5 times higher in betel quid chewers compared to non-chewers (OR = 5.5, 95% CI: 3.1–8.9; p < 0.001). Conclusion This study emphasizes the association between betel quid chewing and the development of OPMDs. Early detection and intervention, combined with lifestyle changes, could significantly reduce the risk of malignant transformation in individuals with OPMDs.