The synergetic effect of nonthermal plasma and ZnO nanoparticles (NPs) on the degradation efficiency of methylene blue was investigated. First, the ZnO nanoparticles were synthesized via the hydrothermal route; the spherical nanoparticles had diameters of 30–50 nm, as observed with a scanning electron microscope (SEM), and had hexagonal ZnO lattice structures, which was confirmed by both X-ray diffraction (XRD) and Raman spectroscopy. The X-ray-photoemission spectroscopy confirmed the ZnO composition and the presence of oxygen vacancies; meanwhile, the optical band gap energy was 3.17 eV. The optical emission of plasma radiation confirmed the presence of various active plasma species. Second, it was found that the maximum degradation efficiency of MB after 60 min was 85% in plasma alone and increased to 95% when combined with 0.2 gL−1 ZnO; but this decreased to 75% when ZnO loading increased to 0.4 gL−1. These results clearly show that combining plasma with the right amount of ZnO is a promising advanced oxidation technique as it provides an additional source of hydroxyl radicals and, at the same time, a source of photons that can excite the ZnO catalyst. The degradation mechanism for plasma alone and the plasma in combination with ZnO was presented.