High concentration N-methyldiethanolamine (MDEA)-containing wastewater with strong alkaline, high chemical oxygen demand (COD), and toxic organics, cannot be directly treated by biochemical process. In this paper, effect of operation parameters (temperature, reaction pressure and residence time) on removal ratio of COD and MDEA was investigated by catalytic wet air oxidation (CWAO) over commercial activated carbon (AC). The degradation pathway of MDEA in the CWAO was proposed. The results showed that the concentration of MDEA, COD, total organic carbon (TOC), and total nitrogen (TN) were 18.92, 61.2, 21.34 and 5.65 g·L−1, respectively. The contribution rate of MDEA concentration to COD in the wastewater reached up to 89.8%. The removal ratio of MDEA and COD exceeded 98% and ∼90% at temperature of 230 °C, reaction pressure of 5.0 MPa and residence time of 90 min for 168 h continuous running, respectively. The surface carboxylic acid groups of AC played a key role in the formation of hydroxyl radicals (·OH), due to the O2 was adsorbed by the carboxyl groups on the surface of AC to form ·OH, and the ·OH then attacked the CN bond of the MDEA to generate other intermediate products, and then these intermediate products was further oxidized to NH4+, CO2 and H2O. This work provides a promising pretreatment technology of high concentration MDEA-containing wastewater.