Interest in using various nanoparticle catalysts to activate H2O2 with light for organic contaminant and wastewater treatment is steadily increasing. We successfully synthesized magnetically recoverable Cu0.5Mn0.5Fe2O4 nanoparticles using a simple co-precipitation method followed by melamine-assisted calcination. Material characterization revealed that melamine acted as a coordinating agent during the calcination process that promoted a ferrite structure. Copper (Cu)-substitution effectively decreased material aggregation and promoted catalytic activities. Cu0.5Mn0.5Fe2O4 nanoparticles showed outstanding catalytic performance on several organic contaminants (87.6–100.0% removal within 2 h). Using oxytetracycline (OTC) as a surrogate wastewater constituent, we found that the hydroxyl radical (•OH) and superoxide anions (•O2−) were the active radical species involved in OTC degradation. Cu0.5Mn0.5Fe2O4 nanoparticles exhibited excellent photo-Fenton catalytic ability in real wastewater and demonstrated high material stability, even after four consecutive uses (i.e., fourth cycle). In a pilot-scale experiment (10 L), we provide proof that our rigorous treatment system was able to remove remnant OTC, TOC, and also any available colloidal particles to only 1 NTU. Ecotoxicity studies using an aquatic plant (Hydrilla verticillata) and zooplankton revealed that treated water could be reused in various ratios. Furthermore, at 5% of treated water, rapid leaf recovery and a significant increase in rotifer numbers were reported. These observations support the use of Cu0.5Mn0.5Fe2O4/H2O2/light as an efficient and environmentally friendly catalytic system for treatment of organic contaminants, and a radical generating mechanism is proposed.