In this work, a novel P-doped Fe2O3-TiO2 mixed oxide was successfully prepared by a microwave assisted sol-gel method. The synthesized catalyst was characterized by N-2 physisorption, SEM, XRD, XPS, and FTIR, UV-vis DRS, and PL spectroscopies. The iron and phosphorus content in the catalyst samples were quantified by AAS and ICPOES, respectively. The photocatalytic activity of P-doped Fe2O3-TiO2 powders were evaluated in the photocatalytic degradation of sulfamethazine (SMTZ). The Box Behnken design (BBD) and response surface methodology (RSM) were applied for modeling the effect and optimizing of the operational parameters levels on the degradation percentage of SMTZ. The complete degradation and mineralization percentage of 30% of SMTZ solution at pH 9 was achieved within 300 min of reaction, with the optimum P doping amount of 1.2 wt % and 1.25 g/L of catalyst loading. The 1.2 wt % P-doped Fe2O3-TiO2 mixed oxide showed considerably higher photocatalytic activity than Fe2O3-TiO2 or TiO2. This enhanced performance could be attributed to the small crystallite size, narrow band gap, high specific surface area and increased number of surface hydroxyls on TiO2 nanoparticles. Additionally, the stability and reusability of this catalyst was demonstrated during three cycles of SMTZ degradation.