•HDP reactor formed plasma discharges in both electrodes with a single power source.•PAW was generated with high energy efficiency and a very fast inactivation rate.•Decreasing the orifice diameter of the HPD reactor increased the energy efficiency.•Increasing salinity enhanced the energy efficiency to 0.181 mol·kW−1·h−1.•5.18-log10 reduction of Escherichia coli inactivation was achieved in 30 s. Plasma-activated water (PAW), an emerging and cost-effective disinfectant produced from the interaction between non-thermal plasma and water, was generated with a newly designed hybrid plasma discharge (HPD) reactor. The HPD reactor produces two simultaneous plasma discharges within one power source, one from the high-voltage electrode above the liquid surface, and the other from the ground electrode enclosed in a quartz tube, allowing the air to flow through the side of the ground electrode and injecting plasma bubbles into the liquid. The simulated distributions of electric field indicated that high electric fields were induced around both the high voltage and ground electrodes, at high input voltages, explaining the plasma discharges observed on both electrodes. The PAW generated via the HPD reactor achieved a high RONS energy efficiency of 1.81 × 10-1 mol·kW−1·h−1 and a high inactivation against Escherichia coli of 5.18-log10 reduction in 30 s of contact time, outperforming reported literature studies, which require minutes or hours to achieve similar inactivation. The effect of the number and size of orifices in the bubble column of the HPD reactor was studied, as well as the effect of the liquid volume (from 0.5 to 2 L), and salinity (from 0 to 8 mM NaCl). The Escherichia coli in PAW was further analysed by TEM and DNA leakage showing that PAW damaged the cell membrane. This hybrid plasma discharge reactor can be the base of producing disinfectant PAW in larger volume for the agriculture, biomedical, food and water treatment industries.