Water pollution is one of the most significant problems of the current century. With the increase in medicine availability and use, pharmaceutical pollutants such as antibiotics become more prevalent in natural environments with potentially negative impact. In this study, a pulsed corona discharge was investigated as a possible treatment method of water contaminated with amoxicillin. Two system configurations were used: plasma and plasma-ozonation. In order to better grasp the effect of system and water matrix on degradation, different pulse widths, solutions pH and conductivity values, as well as the nature of the dissolved salts were investigated. Decreasing the pulse width from 300 ns to 106 ns (full width at half maximum) led to almost a two-fold increase in energy yield at 50 % pollutant removal, and the addition of the ozonation reactor resulted six times enhancement in efficiency. While the water matrix had little impact on amoxicillin degradation, the buffering capacity of carbonates has proven beneficial by preventing pH decrease during treatment. Under optimum conditions, the energy yield was 57 g/kWh at 93% removal of amoxicillin in tap water. A number of 26 potential degradation products have been identified, resulting from hydroxylation of the benzene ring, oxidation of the thioester and amine groups, hydrolysis, and cleavage of the benzene, β-lactam and thiazole rings, along with fragmentation of the resulting compounds. All but seven degradation intermediates are completely removed by extending treatment duration to 60 minutes and the persistent ones are less toxic than the parent compound.