This study aimed to investigate the association between lifetime occupational history and risk of buccal mucosa cancer (BMC). We utilized a multi-centric, hospital-based case-control study across five centres of Tata Memorial Centre, Mumbai, India. Cases included men aged 20–75-years with histological confirmed primary cancer of the buccal mucosa. Visitor controls were frequency matched to cases for age (10 years interval) and current residential zone. Study participants were interviewed face-to-face. Logistic regression was performed to estimate odds ratio (OR) and 95 % confidence intervals (CI). Among ever employed males, we identified 1969 BMC cases and 2145 controls. We observed an increased risk of BMC in ‘Craft and Related Trades Workers’ (OR 1.37; 95 % CI 1.13–1.65), ‘Plant and Machine Operators and Assemblers’ (OR: 1.26; 95 % CI 1.01–1.56), and ‘Elementary Occupations’ (OR:1.33; 95 % CI 1.12–1.58). More specifically, the increased risk was observed for ‘Metal, Machinery and Related Trades Workers’, ‘Handicraft and Printing Workers’, ‘Drivers and Mobile Plant Operators’, and ‘Laborers in Mining, Construction, Manufacturing and Transport’. Our findings suggest that certain occupations may be at a higher risk of BMC. Some fraction of BMC can be prevented by reducing exposure to hazardous agents used in these occupations. Further research is needed to identify which exposures are responsible for the increased risk. Moreover, tobacco control and early detection activities can be focused towards these occupations as tobacco consumption is also high in them, which may also be the reason for increased risk observed in these groups. •We observed an increased risk of BMC in ‘Craft and Related Trades Workers’, ‘Plant and Machine Operators and Assemblers’, and ‘Elementary Occupations’.•More specifically, the increased risk was observed for ‘Metal, Machinery and Related Trades Workers’, ‘Handicraft and Printing Workers’, ‘Drivers and Mobile Plant Operators’, and ‘Labourers in Mining, Construction, Manufacturing and Transport’.•Even though we adjusted for tobacco use, the rates of chewing were high in these occupations, which may explain some of the associations that we observed.