Levofloxacin (LEV) residue is one of the key issues with livestock wastewater, posing a threat to aquatic ecosystems and human health. Herein, MoS2 sponge (MS) co-catalyst was synthesized using a simple impregnation method to construct a MS/Fenton system. Under suitable conditions, MS/Fenton could achieve 95.8 % LEV degradation in 30 min, with a reaction rate constant 9.75 times higher than that of Fenton. The results of the reactive oxygen species identification and material characterization indicated that the massive decomposition of H2O2 generated ROS (•OH and 1O2) and accelerated Fe2+ regeneration were the main factors for pollutant removal. MS/Fenton performed well in various aqueous matrices, reflecting excellent adaptability and anti-interference performance. MS was structurally stable with minimal Mo leaching after the reaction. Furthermore, an external circulation packed-bed reactor was designed for application feasibility verification of the system. The system demonstrated excellent removal efficiency during 20 days of continued operation (without MS regeneration). In addition, MS/Fenton demonstrated a remarkable purification effect on real livestock wastewater. This study offered new insights for the large-scale preparation of recyclable co-catalysts, and the constructed long-acting and stable MS/Fenton system and reactor provide a reference for the green and efficient treatment of practical wastewater.