The photocatalytic activity of natural sphalerite (the main mineral ore of ZnS) is relatively low in the absence of sacrificial donors. Present work focuses on the improvement of the photocatalytic activity of a natural sphalerite obtained from Abuni deposit, Nigeria, via calcination at 600°C, 700°C and 800°C. The raw and calcined natural sphalerite samples were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and specific surface area analysis. The activity of the raw and calcined samples was evaluated using photocatalytic decolorization of methyl orange (MO) as the model reaction. The kinetics of photocatalytic decolorization of MO on the raw and calcined natural sphalerite samples was fitted to the pseudo-first order approximation of the Langmuir–Hinshelwood model. The photocatalytic activity of the natural sphalerite was doubled upon calcination at 700°C. The natural sphalerite calcined at 700°C is also more active than the ones calcined at 600°C and 800°C due to the combined effects of chemical composition, crystallite size, specific surface area and oxygen vacancies.