Drought frequency is increasing in many parts of the world and may enhance tree decline and mortality. The underlying physiological mechanisms are poorly understood, however, particularly regarding chronic effects of long-term drought and the response to increasing temperature and vapor pressure deficit (VPD). We combined analyses of radial growth and stable carbon isotope ratios (δ¹³C) in tree rings in a mature Scots pine (Pinus sylvestris L.) forest over the 20th century to elucidate causes of tree mortality in one of the driest parts of the European Alps (Pfynwald, Switzerland). We further compared trees that have recently died with living trees in a 10-year irrigation experiment, where annual precipitation was doubled. We found a sustained growth increase and immediate depletion of δ¹³C values for irrigated trees, indicating higher stomatal conductance and thus indeed demonstrating that water is a key limiting factor for growth. Growth of the now-dead trees started declining in the mid-1980s, when both mean temperature and VPD increased strongly. But growth of these trees was reduced to some extent already several decades earlier, while intrinsic water-use efficiency derived from δ¹³C values was higher. This indicates a more conservative water-use strategy compared with surviving trees, possibly at the cost of low carbon uptake and long-term reduction of the needle mass. We observed reduced climatic sensitivity of raw tree-ring δ¹³C for the now-dead in contrast to surviving trees, indicating impaired stomatal regulation, although this difference between the tree groups was smaller after detrending the data. Higher autocorrelation and a lower inter-annual δ¹³C variability of the now-dead trees further indicates a strong dependence on (low) carbon reserves. We conclude that the recent increase in atmospheric moisture demand in combination with insufficient soil water supply was the main trigger for mortality of those trees that were weakened by long-term reduced carbon uptake.