In Bangladesh’s south-central coastal zone, there is considerable potential to intensify crop production by growing dry winter season ‘Boro’ rice, maize, wheat, pulses and oilseeds using irrigation from southward flowing and predominantly freshwater rivers. However, the impacts of surface water withdrawal for sustained irrigation and its safe operating space remain unclear. We used field measurements and simulation modeling to investigate the effects of irrigation water withdrawal for Boro rice–the most water-consumptive crop–on river water flow and salinity under different climate change and river flow scenarios. Under the baseline conditions, about 250,000 ha could potentially be irrigated with river water that has salinity levels below 2 dS/m. The impact on river water salinity would be minimal, and only between 0.71 to 1.12% of the cropland would shift from the 0–2 dS/m class to higher salinity levels. Similarly, for the moderate climate change scenario (RCP 4.5) that forecasts a sea level rise of 22 cm in 2050, there would be a minor change in water flow and salinity. Only under the extreme climate change scenario (RCP 8.5), resulting in a sea level rise of 43 cm by 2050 and low flow conditions that are exceeded in 90% of the cases, the 2 dS/m isohaline would move landward by 64 to 105 km in March and April for the Tentulia and Buriswar Rivers. This would expose an additional 36.6% of potentially irrigable cropland to salinity levels of 2 to 4 dS/m. However, Boro rice will already be well established by that time and can tolerate greater levels of salinity. We conclude that there is considerable scope to expand irrigated crop production without negatively exposing the cropland and rivers to detrimental salinization levels while preserving the ecosystem services of the rivers.