Carbamazepine (CBZ) is a typical psychotropic pharmaceutical which is one of the most commonly detected persistent pharmaceuticals in the environment. The degradation of CBZ in the aqueous solution was studied by a direct current (DC) gas-liquid phase discharge plasma combined with different catalysts (H2O2 or Fe2+) in this study. The concentrations of reactive species (H2O2, O3, and NO3− ) and •OH radical yield in the liquid were measured during the discharge process. The various parameters that affect the degradation of CBZ, such as discharge powers, initial concentrations, initial pH values, and addition of catalysts, were investigated. The results indicated that a discharge power at 35.7W achieved the optimal balance on the degradation effect and energy efficiency, and both acidic and alkaline solution conditions were conducive to promoting the degradation of CBZ. Both H2O2 and Fe2+ at low concentration (10–100mg/L of Fe2+, 0.05–2.0 mmol/L of H2O2) were observed contributing to the improvement of the CBZ degradation rate, while the promotional effect of CBZ degradation was weakened even inhibition would occur at high concentrations (100–200 mg/L of Fe2+, 2.0–5.0 mmol/L of H2O2). Furthermore, the total organic carbon (TOC) removal efficiency of CBZ was up to 67.1% in the plasma/Fe2+ (100mg/L) system at 48 min, which suggested a high mineralization efficiency on CBZ could be achieved by employing Fe2+ as a catalyst. Based on the intermediate products identified by UPLC–MS, the possible degradation pathways were proposed. Finally, the growth inhibition assay with E. coli showed that the toxicity of plasma/Fe2+-treated CBZ solution decreased and a relatively low solution toxicity could be achieved. Thus, the plasma/catalyst could be an effective technology for the degradation of pharmaceuticals in aqueous solutions.