In this study, a multi-pin-to-plate negative glow discharge reactor was employed to degrade the hazardous compound, trichloroethylene (TCE). The response surface methodology (RSM) was applied to examine the influences of various process factors (relative humidity (RH), gas flow rate, and discharge power) on the TCE decomposition process, with regard to the TCE removal efficiency, CO2 and CO selectivities. The variance analysis was used to estimate the significance of the single process factors and their interactions. It has been proved that the discharge power had the utmost influential impact on the TCE removal efficiency, CO2 and CO selectivities, subsequently the gas flow rate, and finally RH. Under the optimal conditions with 20.83% RH, 2 W discharge power and 0.5 L·min–1 gas flow rate, the optimal TCE removal efficiency (86.05%), CO2 selectivity (8.62%), and CO selectivity (15.14%) were achieved. In addition, a possible TCE decomposition pathway was proposed based on the investigation of byproducts identified in the exhaust gas of the NTP reactor. This work paves a way for the control of chlorinated volatile organic compounds.