One of the most commonly produced industrial chemicals worldwide, bisphenol A (BPA), is used as a precursor in plastics, resins, paints, and many other materials. It has been proved that BPA can cause long-term adverse effects on ecosystems and human health due to its toxicity as an endocrine disruptor. In this study, we developed an integrated MnO2/UV/persulfate (PS) process for use in BPA photocatalytic degradation from water and examined the reaction mechanisms, degradation pathways, and toxicity reduction. Comparative tests using MnO2, PS, UV, UV/MnO2, MnO2/PS, and UV/PS processes were conducted under the same conditions to investigate the mechanism of BPA catalytic degradation by the proposed MnO2/UV/PS process. The best performance was observed in the MnO2/UV/PS process in which BPA was completely removed in 30 min with a reduction rate of over 90% for total organic carbon after 2 h. This process also showed a stable removal efficiency with a large variation of pH levels (3.6 to 10.0). Kinetic analysis suggested that 1O2 and SO4•− played more critical roles than •OH for BPA degradation. Infrared spectra showed that UV irradiation could stimulate the generation of –OH groups on the MnO2 photocatalyst surface, facilitating the PS catalytic degradation of BPA in this process. The degradation pathways were further proposed in five steps, and thirteen intermediates were identified by gas chromatography-mass spectrometry. The acute toxicity was analyzed during the treatment, showing a slight increase (by 3.3%) in the first 30 min and then a decrease by four-fold over 2 h. These findings help elucidate the mechanism and pathways of BPA degradation and provide an effective PS catalytic strategy.