Seed priming is an effective and novel technique and the use of eco-friendly biological agents improves the physiological functioning in the vegetative stage of plants. This procedure ensures productivity and acquired stress resilience in plants against adverse conditions without contaminating the environment. Though the mechanisms of bio-priming-triggered alterations have been widely explained under induvial stress conditions, the interaction of combined stress conditions on the defense system and the functionality of photosynthetic apparatus in the vegetative stage after the inoculation to seeds has not been fully elucidated. After Bacillus pumilus inoculation to wheat seeds (Triticum aestivum), three-week-old plants were hydroponically exposed to the alone and combination of salt (100 mM NaCl) and 200 μM sodium arsenate (Na2HAsO4·7H2O, As) for 72 h. Salinity and As pollutant resulted in a decline in growth, water content, gas exchange parameters, fluorescence kinetics and performance of photosystem II (PSII). On the other hand, the seed inoculation against stress provided the alleviation of relative growth rate (RGR), relative water content (RWC) and chlorophyll fluorescence. Since there was no effective antioxidant capacity, As and/or salinity caused the induction of H2O2 accumulation and thiobarbituric acid reactive substances content (TBARS) in wheat. The inoculated seedlings had a high activity of superoxide dismutase (SOD) under stress. B. pumilis decreased the NaCl-induced toxic H2O2 levels by increasing peroxidase (POX) and enzymes/non-enzymes related to ascorbate-glutathione (AsA-GSH) cycle. In the presence of As exposure, the inoculated plants exhibited an induction in CAT activity. On the other hand, for H2O2 scavenging, the improvement in the AsA-GSH cycle was observed in bacterium priming plants plus the combined stress treatment. Since B. pumilus inoculation reduced H2O2 levels against all stress treatments, lipid peroxidation subsequently decreased in wheat leaves. The findings obtained from our study explained that the seed inoculation with B. pumilus provided an activation in the defense system and protection in growth, water status, and gas exchange regulation in wheat plants against the combination of salt and As.