Introduction: Oral mucosal lesions (OML) are significant public health concerns, particularly in populations with high tobacco and alcohol use. Handloom factory workers, due to their occupational environment and socio-economic factors, are prone to such habits. This study aims to evaluate the prevalence of OML among handloom factory workers in Panipat, Haryana, and its association with smoking, smokeless tobacco, and alcohol consumption. Materials and methods: A cross-sectional study was conducted among 400 handloom workers aged 18–68 years. Participants were classified based on their habits: Smoking, smokeless tobacco use, alcohol consumption, or combinations of these substances. Detailed oral examinations were performed to identify OML, and statistical analysis was conducted to assess the relationship between substance use and lesion prevalence. Results: Of the 400 participants, 28.25% reported using one or more substances. Smoking and alcohol consumption were predominantly seen in males, while smokeless tobacco use was more common in females. The overall prevalence of OML was 17.5%, with frictional keratosis and tobacco pouch keratosis being the most frequently observed lesions. Smokeless tobacco users exhibited a higher prevalence of OML, including tobacco pouch keratosis and leukoplakia. Younger workers (18–40 years) were more affected. A significant association was found between substance use and OML, with 59.9% of habit-users presenting lesions compared to 1.6% of nonusers. Conclusions: This study highlights the considerable burden of OML among handloom workers, particularly among those engaging in smokeless tobacco and alcohol consumption. Public health initiatives focusing on education and cessation strategies are crucial to mitigate this risk.