This study aimed to investigate the thyroid disrupting effects of multiple metals exposure with comprehensive investigation from the thyroid parenchyma to hormonal function. In this prospective cohort study of in-service staff of the Baoding Power Supply, we found that arsenic was negatively associated with total thyroxine (TT4) [OAs = -0.075, 95% confidence interval (CI): -0.129, -0.020, Padj = 0.04]. Similarly, selenium was negatively correlated with TT4 (OSe = -0.134, 95% CI: -0.211, -0.058, Padj < 0.01) and peripheral deiodinase activity (GT) (OSe = -0.133, 95% CI: -0.210, -0.056, Padj = 0.01). With respect to strontium, there were positive associations of strontium with thyroid-stimulating hormone (OSr = 0.263, 95% CI: 0.112, 0.414, Padj = 0.01), and negative associations of strontium with TT4 (OSr = -0.099, 95% CI: -0.150, -0.048, Padj < 0.01) and GT (OSr = -0.102, 95% CI: -0.153, -0.050, Padj < 0.01). We also observed negative associations of metal mixtures with TT4 and GT and potential interactions. Increased risks of thyroid nodule associated with aluminum, cobalt and nickel were also observed. Our findings suggest that multiple metals exposure leads to a multi-pronged assault to thyroid from the thyroid parenchyma to hormonal function. Future large-scale prospective cohort studies of general population and experimental studies were warranted.