The 2003 and 2012 summer seasons were among the warmest and driest of the last 200 years over southeastern Europe, and in particular in the Karst region (northeastern Italy). Starting from winter-spring 2013, several black pines (Pinus nigra J.F. Arnold) suffered crown die-back. Declining trees occurred nearby individuals with no signs of die-back, raising hypotheses about the occurrence of individual-specific hydraulic strategies underlying different responses to extreme drought. We investigated possible processes driving black pine decline by dendrochronological and wood anatomical measurements, coupled with analysis of tree-ring carbon (δ¹³C) and oxygen (δ¹⁸O) isotopic composition in healthy trees (H) and trees suffering die-back (D). Die-back trees showed higher growth rates than H trees at the beginning of the last century, but suffered important growth reduction following the dry summers in 2003 and 2012. After the 2012 drought, D trees produced tracheids with larger diameter and greater vulnerability to implosion than H ones. Healthy trees had significantly higher wood δ¹³C than D trees, reflecting higher water-use efficiency for the surviving trees, i.e., less water transpired per unit carbon gain, which could be related to lower stomatal conductance and a more conservative use of water. Relatively high δ¹⁸O for D trees indicates that they were strongly dependent on shallow water sources, or that they sustained higher transpiration rates than H trees. Our results suggest that H trees adopted a more conservative water-use strategy under drought stress compared with D trees. We speculate that this diversity might have a genotypic basis, but other possible explanations, like different rooting depth, cannot be ruled out.