Rhizosphere is the battlefield of beneficial and harmful (so called phytopathogens) microorganisms. Moreover, these microbial communities are struggling for their existence in the soil and playing key roles in plant growth, mineralization, nutrient cycling and ecosystem functioning. In the last few decades, some consistent pattern have been detected so far that link soil community composition and functions with plant growth and development; however, it has not been studied in detail. AM fungi are model organisms, besides potential role in nutrient cycling; they modulate biochemical pathways directly or indirectly which lead to better plant growth under biotic and abiotic stress conditions. In the present investigations, we have elucidated the AM fungi-mediated activation of plant defense responses againstMeloidogyne graminicolacausing root-knot disease in direct seeded rice (Oryza sativaL.). The study describes the multifarious effects ofFunneliformis mosseae, Rhizophagus fasciculatus, andRhizophagus intraradicesinoculated individually or in combination under glasshouse conditions in rice plants. It was found thatF. mosseae, R. fasciculatusandR. intraradiceswhen applied individually or in combination modulated the biochemical and molecular mechanisms in the susceptible and resistant inbred lines of rice. AM inoculation significantly increased various plant growth attributes in plants with simultaneous decrease in the root-knot intensity. Among these, the combined application ofF. mosseae, R. fasciculatus, andR. intraradiceswas found to enhance the accumulation and activities of biomolecules and enzymes related to defense priming as well as antioxidation in the susceptible and resistant inbred lines of rice pre-challenged withM. graminicola. The application ofF. mosseae, R. fasciculatusandR. intraradices, induced the key genes involved in plant defense and signaling and it has been demonstrated for the first time. Results of the present investigation advocated that the application ofF. mosseae, R. fasciculatusandR. intraradices, particularly a combination of all three, not only helped in the control of root-knot nematodes but also increased plant growth as well as enhances the gene expression in rice. Thus, it proved to be an excellent biocontrol as well as plant growth-promoting agent in rice even when the crop is under biotic stress of the root-knot nematode,M. graminicola.