Exploitation of low-quality water or irrigation of field crops with saline water in salt-affected soil is a critical worldwide challenge that rigorously influences agricultural productivity and sustainability, especially in arid and semiarid zones with limited freshwater resources. Therefore, we investigated a synergistic amendment strategy for salt-affected soil using a singular and combined application of plant growth-promoting rhizobacteria (PGPR at 950 g ha−1; Azotobacter chroococcum SARS 10 and Pseudomonas koreensis MG209738) and silica nanoparticles (SiNPs) at 500 mg L−1 to mitigate the detrimental impacts of irrigation with saline water on the growth, physiology, and productivity of barley (Hordum vulgare L.), along with soil attributes and nutrient uptake during 2019/2020 and 2020/2021. Our field trials showed that the combined application of PGPR and SiNPs significantly improved the soil physicochemical properties, mainly by reducing the soil exchangeable sodium percentage. Additionally, it considerably enhanced the microbiological counts (i.e., bacteria, azotobacter, and bacillus) and soil enzyme activity (i.e., urease and dehydrogenase) in both growing seasons compared with the control. The combined application of PGPR and SiNPs alleviated the detrimental impacts of saline water on barley plants grown in salt-affected soil compared to the single application of PGPR or SiNPs. The marked improvement was due to the combined application of PGPR and SiNPs, which enhanced the physiological properties (e.g., relative chlorophyll content (SPAD), relative water content (RWC), stomatal conductance, and K/Na ratio), enzyme activity (superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX)), and yield and yield-related traits and nutrient uptake (N, P, and K) of barley plants. Moreover, the Na+ content, hydrogen peroxide (H2O2) content, lipid peroxidation (MDA), electrolyte leakage (EL), and proline content were reduced upon the application of PGPR + SiNPs. These results could be important information for cultivating barley and other cereal crops in salt-affected soil under irrigation with saline water.