The Elbe River basin, located in Germany and the Czech Republic, is vulnerable to changing climate extremes and has experienced multiple natural hazards over the years. Therefore, assessing the impacts of climate change on extreme events across the basin is vital to adapt and improve resiliency. Unfortunately, data on variations of climate extremes usually have a very coarse spatial resolution, which limits any regional application. Thus, to improve the quality and availability of climate extreme data, we estimated climate indices mostly from the Expert Team on Climate Change Detection Monitoring and Indices (ETCCDI). The indices were based on temperature, precipitation, and agrometeorology. They were estimated on a regional scale using an ensemble of high-resolution (12.5 km) climate model data. Two different climate scenarios, rcp26 and rcp85, were considered. The eight climate indices estimated in this study (1) help better understand the variation in climate extreme events, (2) identify vulnerable areas, and (3) analyse their impact on natural resources (e.g., agriculture). The results showed that by the end of this century, temperature-based extremes will increase with minimal spatial variation for summer months, while precipitation-based extremes show that conditions which promote flood events will increase in the headwater regions located in the South of the basin. Additionally, agrometeorological indicators imply that factors favourable for agricultural processes will become more common, but their trend and seasonal analysis show extreme events will hinder the application of best farming practices. Lastly, policy recommendations for adaptation measures (e.g., green infrastructure) have been highlighted in this study to address different climate risks, enabling resilient resource management across the basin.