The burgeoning shortage of freshwater resources coerced Indian farmers to use poor-quality water for crop production in order to meet the growing and diversified food demands. Such conditions are likely to become more alarming in the future. Therefore, the present study was undertaken to identify the ideal crop combinations and agronomic practices which might give good yield under stressed conditions. An on-field experiment was conducted for two years to determine the suitable combinations of organic manure (farmyard manure @ 10 t/ha, vermicompost @ 2.5 t/ha and biogas slurry @ 2.5 t/ha), chemical fertilizers (75%, 100% and 125% recommended dose of fertilizer (RDF)) and microbial inoculants (Azotobacter chroococcum and Biomix) for enhancing productivity of the pearl millet–wheat cropping system irrigated with saline water. A significant improvement in the yield of pearl millet and wheat crops was obtained by integrated application of nutrients compared with untreated control and RDF treatments. Furthermore, a decrease in soil EC and pH, and an increase in organic carbon were noticed. A marked improvement in the availability of nitrogen, phosphorus, potassium, calcium and magnesium status in the soil and reduction in sodium content resulted as an outcome. The T10 combination (RDF + VC + Biomix) was found to be the most suitable for profitable production of pearl millet and wheat crops under saline conditions of northwestern India. © 2020