Prospective studies on occupational dermatoses in the general working population are sparse. This study investigated prospectively the impact of self-reported occupational exposure to chemicals and physical factors on the risk of skin problems. The cohort comprised respondents drawn randomly from the general population in Norway, who were registered employed in 2006 and 2009 (n = 6,745). Indoor dry air (odds ratio (OR) 1.3; 95% confidence interval (95% CI) 1.1–1.6) was a significant baseline predictor of skin problems at follow-up, whereas exposure to cleaning products (OR 1.7; 95% CI 1.2–2.5), water (OR 1.4; 95% CI 1.1–1.9) and indoor dry air (OR 1.6; 95% CI 1.1–2.1) at both measurement time-points was significantly associated with skin problems. The population risk attributable to these factors was 16%. This study quantified the contribution of occupational exposure factors to skin problems in the general working population of Norway.