The current study was conducted to isolate, characterize and reveal the impact of native soil microorganisms on durum wheat cultivars (Tejas and Poshan). Three isolates, Candida tropicalis (PY1), Actinomucor elegans (PT1) and Delftia lacustris (IS5) were identified on the basis of cultural characteristics and gene sequencing. Strains possessed multiple plant growth-promoting traits (phytohormones, extracellular enzymes, siderophores and mineral solubilization). Isolates (IS5, PY1, PT1, MDRS14 (Bacillus aryabhattai) and MDSR34 (Bacillus endophyticus) were co-cultured and confirmed to be compatible. The microcosm experiment was conducted with microbial inoculant treatments MI1-MI10, under factorial randomized complete block design with three replications. When compared to the uninoculated control, inoculation of PT1+IS5 in Poshan and MDSR14+MDSR34 in Tejas significantly enhanced the rhizosphere soil characteristics, soil nutrient content, grain nutrient, crop growth parameters, crude protein content, and grain yield for 27.1 and 28.1% in Poshan and Tejas, respectively. On contrary, the phytic acid/Zn (<15) and Fe (<10) decreased in both cultivars. The principal component analysis showed MI5, MI6, MI7, MI8 microbial inoculant treatments to be better for Poshan and MI7 and MI8 for Tejas. Cluster analysis confirmed seed inoculation of culturable microbial strains (MDSR 14 + MDSR 34 and PY1 + PT1) performed better in both cultivars and, thus, have the potential to be exploited as broad-spectrum biofertilizers for durum wheat. The strategy utilizing these isolated microorganisms could be vital to boost durum wheat yield and can be recommended to improve the wheat productivity.