The photocatalytic degradation of minocycline was studied by using polyvinylidene fluoride–polyvinylpyrrolidone–TiO₂ (PVDF–PVP–TiO₂) fiber mats prepared by an electrospinning technology. The influences of the TiO₂ dosage, minocycline concentrations, inorganic anions, pH values, and dissolved organic matter (DOM) concentrations on the degradation kinetics were investigated. A mass of 97% minocycline was degraded in 45 min at 5% TiO₂ dosage. The corresponding decomposition rate constant was 0.069 min⁻¹. The inorganic anions affected the minocycline decomposition in the order of HCO₃⁻ > Cl⁻ > SO₄²⁻ > NO₃⁻, which was confirmed by the results of electron spin resonance (ESR) spectra. The lowest electrical energy per order (E_EO) was 6.5 Wh/L. Over five cycles, there was no change in the photocatalytic performance of the degrading minocycline. Those investigations suggested that effective degradation of minocycline could be reached in the PVDF–PVP–TiO₂ fiber mats with a low energy consumption, good separation and, good recovery. Three photocatalytic decomposition pathways of minocycline were proposed: (i) hydroxyl substitution of the acylamino group; (ii) hydroxyl substitution of the amide group, and (iii) a cleavage of the methyl groups and further oxidation of the amino group by OH. Potential risks caused by TP159 and TP99 should not be ignored, while the TP90 are nontoxic. Tests indicated that the toxicity of the photocatalytic process may be persistent if minocycline and its products were not mineralized completely.