Ethylenediaminetetraacetic acid (EDTA) can form very stable complexes with heavy metal ions, greatly inhibiting conventional metal-removal technologies used in water treatment. Both the oxidation of EDTA and the reduction of metal ions in metal-EDTA systems via the microwave-enhanced Fenton reaction followed by hydroxide precipitation were investigated. The Cu(II)-Ni(II)-EDTA, Cu(II)-EDTA and Ni(II)-EDTA exhibited widely different decomplexation efficiencies under equivalent conditions. When the reaction reached equilibrium, the chemical oxygen demand was reduced by a microwave-enhanced Fenton reaction in different systems and the reduction order from high to low was Cu(II)-Ni(II)-EDTA ≈ Cu(II)-EDTA > Ni(II)-EDTA. The removal efficiencies of both Cu(2+) and Ni(2+) in Cu-Ni-EDTA wastewaters were much higher than those in a single heavy metal system. The degradation efficiency of EDTA in Cu-Ni-EDTA was lower than that in a single metal system. In the Cu-Ni-EDTA system, the microwave thermal degradation and the Fenton-like reaction created by Cu catalyzed H2O2 altered the EDTA degradation pathway and increased the pH of the wastewater system, conversely inhibiting residual EDTA degradation.