Plant growth and crop productivity under unfavorable environmental challenges require a unique strategy to scavenge the severely negative impacts of these challenges such as soil salinity and water stress. Compost and plant growth-promoting rhizobacteria (PGPR) have many beneficial impacts, particularly in plants exposed to different types of stress. Therefore, a field experiment during two successive seasons was conducted to investigate the impact of compost and PGPR either separately or in a combination on exchangeable sodium percentage (ESP), soil enzymes (urease and dehydrogenase), wheat physiology, antioxidant defense system, growth, and productivity under deficient irrigation and soil salinity conditions. Our findings showed that exposure of wheat plants to deficit irrigation in salt-affected soil inhibited wheat growth and development, and eventually reduced crop productivity. However, these injurious impacts were diminished after soil amendment using the combined application of compost and PGPR. This combined application enhanced soil urease and dehydrogenase, ion selectivity, chlorophylls, carotenoids, stomatal conductance, and the relative water content (RWC) whilst reducing ESP, proline content, which eventually increased the yield-related traits of wheat plants under deficient irrigation conditions. Moreover, the coupled application of compost and PGPR reduced the uptake of Na and resulted in an increment in superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX) activities that lessened oxidative damage and improved the nutrient uptake (N, P, and K) of deficiently irrigated wheat plants under soil salinity. It was concluded that to protect wheat plants from environmental stressors, such as water stress and soil salinity, co-application of compost with PGPR was found to be effective.