Introduction India is one of the leading producers and consumer of tobacco. Additionally, India has one of the highest global prevalence of oral leukoplakia (OL). However, large epidemiological studies from Madhya Pradesh (Central India), the state with maximum consumers of tobacco products in India, are lacking. Objective Thus, we assessed the prevalence of OL among individuals residing in Central India and evaluated its association with age, gender, and history of adverse habits. Methods This was a prospective, cross-sectional study involving 9954 patients visiting the out-patient Department of Oral Medicine and Radiology over a period of 15 months (January 2019 to March 2020). The clinical diagnosis of OL was arrived by exclusion of all the lesions mimicking OL. Univariate and multivariate analyses were performed to assess the association between OL and age, sex, and history of adverse habits. Results The prevalence of OL was 5.6% (557/9954). It was predominant in males (male-to-female ratio=3.9:1) and increased with advancing age. The odds of developing OL was higher among patients aged ≥50 years (OR=1.08; 95%CI: 1.07–1.08, p-value<0.0001), those with history of smoking tobacco (OR=1.32; 95%CI: 1.05–1.68, p-value=0.02), consuming smokeless tobacco (OR=318.60; 95%CI: 101.68–998.30, p-value<0.0001), and alcohol (OR=1.15; 95%CI: 9.0–1.49, p-value=0.269). Females had lower odds of developing OL (OR=0.77; 95%CI: 0.60–0.99, p-value=0.042). Conclusion We observed high prevalence of OL (5.6%). OL was significantly associated with older age, male sex, and tobacco-related adverse habits. While, alcohol consumption may possibly be a risk factor, no statistically significant relation was observed.