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Wheat is the third largest grown crop after maize and rice worldwide. Integrated use of chemical and biofertilizers have the potential to improve crop yield and quality due to their growth-promoting attributes. Therefore, the present study planned to evaluate the effectiveness of endophytic (Paenibacillus sp. strain (ZE11), Bacillus subtilis (ZE15) and Bacillus megaterium (ZE32)) and rhizobacterial strains (Bacillus subtilis (ZR2) Bacillus subtilis (ZR3) and Bacillus megaterium strain (ZR19)), solely and in combination, to increase the productivity of wheat and microbial activity in the rhizosphere. The maximum increase in microbial biomass carbon (44%), available phosphorous (30%), ammonium–nitrogen (24%), nitrate–nitrogen (37%), iron (10%), zinc (11%) and bacterial population (31%) was recorded by co-inoculation of ZE11 + ZR3. Subsequently, co-inoculation of ZE11+ZR3 showed a maximum increase of 31%, 29%, 30%, 27%, 33%, 30%, 25%, 9%, 15%, 9%, 18% and 26% in superoxidase dismutase (SOD), peroxidase dismutase (POD), catalase (CAT), ascorbate peroxidase (APX), polyphenol oxidase (PPO) and peroxidase (POX), grain yield, nitrogen, phosphorous, potassium, iron and zinc in grains, respectively, as compared to uninoculated control. The sole inoculation of ZR19 showed maximum harvest index (45.5%). The sole inoculation of endophytes and rhizobacteria has a significant effect on growth, physiology, and wheat crop yield. However, co-inoculation had a better effect and can be used to develop multi-strain biofertilizer to promote growth and yield of crops.