Thermal plasma is successfully used to degrade the model pharmaceutical wastewater ciprofloxacin (CIP) under submerged operating conditions at atmospheric pressure. The model aqueous solution is prepared for two different concentrations (10 and 25 mg/L) and treated separately at 7 kW discharge power with two different plasma-forming gas compositions, Ar/Air and Ar/CO2. A direct current (DC) hollow cathode plasma torch produces a thermal plasma jet inside the solution. The effect of plasma gas compositions on the CIP degradation process is investigated, and the corresponding degradation and mineralisation efficiencies for different treatment times are systematically compared using high-performance liquid chromatography (HPLC) and total organic carbon (TOC) analysis, respectively. Submerged Ar/CO2 plasma shows higher degradation and mineralisation efficiency than the Ar/Air plasma. Energy yields of 74.32 mg/kWh and 176.98 mg/kWh are achieved for a 5-min treatment by Ar/CO2 submerged thermal plasma at concentrations of 10 mg/L and 25 mg/L, respectively. The degradation of CIP by submerged plasma shows a resemblance with first-order reaction kinetics having reaction rates 0.149 min−1 and 0.073 min−1 for Ar/CO2 and Ar/Air, respectively. Density Functional Theory (DFT) calculations are used to identify the various reactive sites on CIP, and the results are consistent with the formation of various intermediates detected through liquid chromatography-mass spectrometry (LC-MS) analysis. These findings suggest that reactive species formed through thermal and photochemical processes in submerged thermal plasma play a significant role in the degradation of CIP. This study also offers a possible way of using CO2 gas in wastewater treatment using submerged thermal plasma.