All sphalerites from 19 ore deposits were crystallized in cubic phases with various chemical compositions. The substitution of Fe element for Zn ranges from 0.235% to 14.826%, while the substitution of Cd element for Zn ranges from 0.133% to 1.576%. With the change of the Fe element from low to high, the color of natural sphalerite becomes darker and eventually becomes black, and the band gap, which was narrow than pure ZnS, was reduced from 3.18 eV to 2.28 eV, with all response in visible light excitation. The photocatalytic performance indicates that the sample with both lower Fe content and higher Cd content shows the highest activity to degrade Methyl orange (MO). For example, the degradation of MO (30 mg/L) with efficiency reached 82.11% under visible light irradiation for 4 h by natural sphalerite with Fe 4.262% and Cd 1.576% (1 g/L). The Fe content in sphalerite contributed to the band gap value and the range of light spectrum responses, while Cd content affected photocatalytic properties. The results obtained by the authors provide the scientific basis for the profitable utilization of base metal resources like natural sphalerite.