BACKGROUND The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high‐incidence areas. METHODS The authors conducted a population‐based case‐control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self‐reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration‐response relations. RESULTS Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26‐1.68), chemical vapors (OR, 1.37; 95% CI, 1.17‐1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25‐1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30‐1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. CONCLUSIONS Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. LAY SUMMARY The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high‐incidence areas. The authors conducted a population‐based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration‐response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high‐incidence region. Occupational exposures are associated with an increased risk of nasopharyngeal carcinoma, and the association is primarily driven by 14 subtypes of occupational agents. Duration‐response trends are observed with increasing duration of exposure.