Karstic aquifers, because of their conduit system, are susceptible to climate change. Ten karst springs in the Zagros region were selected to investigate the impact of climate change under three CMIP6 scenarios: SSP1-1.9, SSP2-4.5, and SSP5-8.5. This study was conducted in three steps: downscaling climate projection, analyzing spring discharge time series, and introducing a new index to assess the impact of climate change on spring flow rate. Applying LARS-WG6, precipitation was downscaled at 14 stations in the study area. Moreover, time series and trend analysis showed that the selected springs have experienced a decrease in their flow rate. Assuming the covariance function between precipitation and spring discharge is constant, new indices (i.e., IQd, IdQd, and Icc) were introduced to highlight the effect of climate change according to the three scenarios. dQd is the variability of spring discharge from past to future, IdQd is spring discharge variability over the historical data, and Icc is the effect of precipitation and spring discharge change together. Icc has a range from −0.25 to 0.25 below and above, which is indicative that two extreme conditions including the spring dryness and overflow are in effect, respectively. The main results revealed that the degree of impact at each spring is a function of climate change scenarios and hydrogeological characteristics of the karstic systems. A more noticeable negative trend in spring flow rate is observed for the karst springs characterized by a dominant conduit flow regime and low matrix storage, located in the areas with low cumulative rainfall, and has a stronger relationship with precipitation. Based on the results, decisions on the management of karst water resources should be made considering where the springs bear free surface and pressurized flow conditions.