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Complete degradation of mixtures of organic pollutants is a major challenge due to their diverse degradation pathways. In this work, a novel microplasma bubble (MPB) reactor was developed to generate plasma discharges inside small forming bubbles as an effective mean of delivering reactive species for the degradation of the target organic contaminants. The results show that the integration of plasma and bubbles resulted in efficient degradation for all azo, heterocyclic, and cationic dyes, evidenced by the outstanding energy efficiency of 13.0, 18.1 and 22.1 g/kWh with 3 min of processing, in degrading alizarin yellow (AY), orange II (Orng-II) and methylene blue (MB), individually. The MPB treatment also effectively and simultaneously degraded the dyes in their mixtures such as AY + Orng-II, AY + MB and AY + Orng-II + MB. Scavenger assays revealed that the short-lived reactive species, including the hydroxyl (OH) and superoxide anion (O 2 −) radicals, played the dominant role in the degradation of the pollutants. Possible degradation pathways were proposed based on the intermediate products detected during the degradation process. The feasibility of this proposed strategy was further evaluated using other common water pollutants. Reduced toxicity was confirmed by the observed increases in human cell viability for the treated water. This work could support the future development of high performance- and energy-efficient wastewater abatement technologies. Unlabelled Image • A plasma bubble column was developed for pollutant degradation. • Underwater microplasma bubbles facilitated mass transfer of reactive species. • Efficient and simultaneous degradation of dye mixtures was demonstrated. • Outstanding energy efficiency for pollutant degradation was obtained. [ABSTRACT FROM AUTHOR]