The objective of this research was to determine the effect of zinc oxide nanoparticles (ZnONPs) and/or salicylic acid (SA) under arsenic (As) stress on rice (Oryza sativa). ZnONPs are analyzed for various techniques viz., X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). All of these tests established that ZnONPs are pure with no internal defects, and can be potentially used in plant applications. Hence, we further investigated for better understanding of the underlying mechanisms and the extent of ZnONPs and SA induced oxidative stress damages. More restricted plant growth, gas exchange indices, significant reduction in the SPAD index and maximum quantum yield (Fv/Fm) and brutal decline in protein content were noticed in As-applied plants. In contrast, foliar fertigation of ZnONPs and/or SA to As-stressed rice plants lessens the oxidative stress, as exposed by subordinate levels of reactive oxygen species (ROS) synthesis. Improved enzymatic activities of catalase (CAT), peroxidase (POX), and superoxide dismutase (SOD), proline and total soluble protein contents under ZnONPs and SA treatment plays an excellent role in the regulation of various transcriptional pathways participated in oxidative stress tolerance. Higher content of nitrogen (N; 13%), phosphorus (P; 10%), potassium (K; 13%), zinc (Zn; 68%), manganese (Mn; 14%), and iron (Fe; 19) in ZnONPs and SA treated plants under As-stress, thus hampered growth and photosynthetic efficiency of rice plants. Our findings suggest that toxicity of As was conquering by the application of ZnONPs and SA in rice plants.