This study assessed the ability of biofertilizer inoculants containing Rhizobium leguminosarum bv. trifolii to enhance production of rice (Oryza sativa L.) under actual agricultural conditions in the Nile delta. Large-scale field experiments evaluated 5 rice varieties inoculated with 7 endophytic rhizobial strains during 5 growing seasons, including at sites ranked as the world’s highest in rice production. Inoculation with single strains or multi-strain consortia significantly increased grain yield in 19 of the 24 trials. By combining superior rhizobial inoculants with agricultural extension training, grain yield increased up to 47% in farmers’ fields, with an average increase of 19.5%. Data on rice straw production, harvest index and the agronomic fertilizer N-use efficiency also indicated positive agronomic benefits of rhizobial inoculation. These results establish the merit of deploying our biofertilization strategy using selected rhizobial strains to promote rice production capacity while reducing the need for additional chemical N-fertilizer inputs to maintain agricultural sustainability and acceptable production economy. Technology transfer of this important translational research can significantly help to alleviate hunger and meet the nutritional needs of many people in developing countries.