While the physiological and transcriptional response of the host to biotic and abiotic stresses have been intensely studied, little is known about the resilience of associated microbiomes and their contribution towards tolerance or response to these stresses. We evaluated the impact of elevated tropospheric ozone (O3), individually and in combination with Xanthomonas perforans infection, under open-top chamber field conditions on overall disease outcome on resistant and susceptible pepper cultivars, and their associated microbiome structure, function, and interaction network across the growing season. Pathogen infection resulted in a distinct microbial community structure and functions on the susceptible cultivar, while concurrent O3 stress did not further alter the community structure, and function. However, O3 stress exacerbated the disease severity on resistant cultivar. This altered diseased severity was accompanied by enhanced heterogeneity in associated Xanthomonas population counts, although no significant shift in overall microbiota density, microbial community structure, and function was evident. Microbial co-occurrence networks under simultaneous O3 stress and pathogen challenge indicated a shift in the most influential taxa and a less connected network, which may reflect the altered stability of interactions among community members. Increased disease severity on resistant cultivar may be explained by such altered microbial co-occurrence network, indicating the altered microbiome-associated prophylactic shield against pathogens under elevated O3. Our findings demonstrate that microbial communities respond distinctly to individual and simultaneous stressors, in this case, O3 stress and pathogen infection, and can play a significant role in predicting how plant-pathogen interactions would change in the face of climate change.