The impact of climate change on groundwater vulnerability has been assessed in the Pannonian basin over 1961-2070. High-resolution climate models, aquifers composition, land cover, and digital elevation model were the main factors which served to perform the spatial analysis using Geographical Information Systems. The analysis reported here is focused on the long-term period, including three temporal time sets: the past period of 1961-1990 (1990s), the present period of 2011-2040 (2020s), and the future period of 2041-2070 (2050s). During the 1990s, the high and very high areas of groundwater vulnerability were identified in all the central, western, eastern, southeastern, and northern sides of the Pannonian basin. In these areas, the water availability is lower and the pollution load index is high, due to the agricultural activities. The low and very low vulnerability class was depicted in the SouthWest part of the basin and in few locations from the peripheral areas, mainly in the North and West. The medium groundwater vulnerability spreads over the Pannonian basin, but it is more concentrated in the central, South, and SouthWest. The most affected territory is Hungary, while the territories of Slovenia, Croatia, and Bosnia and Herzegovina are less affected. In the present and future periods, the very high groundwater vulnerability increased in areas by 0.74% and 0.87%, respectively. The low class area decreased between the 1990s and the 2020s by 2.33% and it is expected to decrease up to 2.97% in the 2050s. Based on this analysis and the groundwater vulnerability maps, the Pannonian basin appears more vulnerable to climate change in the present and future. These findings demonstrate that the aquifers from Pannonian basin experience high negative effect under climate conditions. In addition, the land cover contributes to this negative status of groundwater resources. The original maps of groundwater vulnerability represent an instrument for water management planning and for research.