This study reports a laboratory investigation of the degradation of microcystin-LR using Fenton (Fe2++H2O2) and Photo-Fenton processes. The effect of hydrogen peroxide concentration on the Fenton reaction rate was investigated at constant Fe2+ concentrations. It was observed that at low concentrations of hydrogen peroxide (0.25–0.5 mM), the extent of microcystin-LR degradation was low, even after prolonged reaction time (up to 600 min). Higher H2O2 concentrations (2.5–5 mM) resulted in higher degradation rates that yielded microcystin-LR degradation as high as 60% in approximately 180 min. However, the highest degradation efficiency of the toxin was achieved during the Photo-Fenton process in which UV radiation was involved. In the Photo-Fenton process, the removal efficiency of microcystin-LR reached 84% in the first 25 min and 100% in approximately 35–40 min of irradiation. These results are encouraging for the application of efficient UV-based advanced oxidation technologies for toxin removal from drinking water sources.