Abstract Objective Iron and steel industry workers are exposed to high levels of inhalable dust particles that contain various elements, including metals, and cause occupational lung diseases. We aim to assess the relationship between occupational dust exposure, systemic inflammation, and spirometric decline in a cohort of Chinese iron and steel workers. Methods We studied 7513 workers who participated in a Health Surveillance program at Wugang Institute for Occupational Health between 2008 and 2017. Time-weighted exposure intensity (TWEI) of dust was quantified based on self-reported dust exposure history, the experience of occupational hygienists, and historical data of dust exposure for workers with certain job titles. A linear mixed-effects model was used for association analyses. Results The average annual change of lung function was − 50.78 ml/year in forced expiratory volume in 1 s (FEV1) and − 34.36 ml/year in forced vital capacity (FVC) in males, and − 39.06 ml/year in FEV1 and − 26.66 ml/year in FVC in females. Higher TWEI prior to baseline was associated with lower longitudinal measurements of FEV1 and FVC but not with their decline rates. Higher WBC and its differential at baseline were associated with lower longitudinal measurements and a more rapid decline of FEV1 and FVC in a dose-dependent monotonically increasing manner. Moreover, the increase of WBC and its differential post-baseline was also associated with a more rapid decline of FEV1 and FVC. Conclusions Our findings support the important role of systemic inflammation in affecting the temporal change of lung function in iron and steel industry workers.