Pomegranate bacterial blight caused by Xanthomonas axonopodis pv. punicae (Xap) is a highly destructive disease. In the absence of host resistance to the disease, we aimed to evaluate the biocontrol potential of endophytic bacteria against Xap. Thus, in this study, we isolated endophytes from pomegranate plants, identified them on the basis of 16S rDNA sequencing, tested them against Xap, and estimated the endophyte-mediated host defense response. The population of isolated endophytes ranged from 3 × 106 to 8 × 107 CFU/g tissue. Furthermore, 26 isolates were evaluated for their biocontrol activity against Xap, and all the tested isolates significantly reduced the in vitro growth of Xap (15.65% ± 1.25% to 56.35% ± 2.66%) as compared to control. These isolates could reduce fuscan, an uncharacterized factor of Xap involved in its aggressiveness. Lower blight incidence (11.6%) and severity (6.1%) were recorded in plants sprayed with endophytes 8 days ahead of Xap spray (Set-III)_ as compared to control plants which were not exposed to endophytes (77.33 and 50%, respectively%) during in vivo evaluation. Moreover, significantly high phenolic and chlorophyll contents were estimated in endophyte-treated plants as compared to control. The promising isolates mostly belonged to the genera Bacillus, Burkholderia, and Lysinibacillus, and they were deposited to the National Agriculturally Important Microbial Culture Collection, India.