The experimental design methodology was used to optimize the experimental parameters of quinoline mineralization by microwave-enhanced catalytic wet peroxide oxidation (CWPO). Initial pH value, temperature, H2O2 dosage, and microwave power were selected as independent variables. The mineralization efficiency approached 83.82% under the optimized conditions: initial pH 6.00, temperature 60 °C, H2O2 dosage 0.09 mol/L, and microwave power 565.10 W. Regression analysis with an R2 value of 0.9867 showed a good agreement between the experimental results and the predicted values. Furthermore, based on the detection and identification of products by gas chromatography mass spectrometry, the oxidation degradation pathways of quinoline were proposed. The energy balance and costs analysis indicated that the total cost of the microwave-enhanced CWPO process for wastewater treatment was 40.60 yuan/m3.