The photolysis of the antibiotic sulphamethoxazole (SMX) using a low pressure ultraviolet (UV) lamp with emission of monochromatic wavelength at 254 nm was evaluated in Milli‐Q water and the effluent from a real sewage treatment plant (STP). The effects of various parameters including initial SMX concentration, solution pH, a variety of inorganic anions (Cl⁻, SO₄ ²⁻, NO₃ ⁻ and HCO₃ ⁻) and humic acid (HA) have been assessed. The results showed that 10 mg L⁻¹ of SMX was removed within 30 min of irradiation in Milli‐Q water. The removal of SMX fitted the pseudo‐first‐order kinetic model with the rate constants in the range of 0.170 to 0.932 min⁻¹ for initial SMX concentrations of 1.0 to 10 mg L⁻¹. Solution pHs of 2.0–5.5 were more favourable for SMX degradation, compared with caustic conditions. On the other hand, slight improvements in SMX degradation in water matrixes with Cl⁻, SO₄ ²⁻ and NO₃ ⁻ anions at 1.0 mM concentration and HA (when used at 5 mg L⁻¹) were observed. However, HCO₃ ⁻ (used at 1.0 mM) and HA (when used at concentrations of 20, 50 and 100 mg L⁻¹) slowed down the degradation rate. The complete degradation of SMX was almost achieved in STP effluent spiked with 10 mg L⁻¹ of SMX after 60 min of irradiation, and the rate constants showed that the turbidity in STP effluent had no significant adverse effect on SMX removal. Total organic carbon was hardly changed even after 8 h of irradiation, showing negligible mineralization of its intermediates under UV₂₅₄ irradiation.