In this study, using a dendrological and isotopic approaches, we investigated the responses to climate of two pure Fagus sylvatica L. stands (Campobraca and Falode) in the southernmost part of the distribution range in southern Italy. The δ13C data were used for calculating the intrinsic water use efficiency (iWUE) as a proxy of the balance between the water and carbon cycles. The results showed that the iWUE of both stands was sensitive to the amount of precipitation during the summer months (negative, significant effect) and to atmospheric CO2 concentration. Growth was sensitive to climate only in the Campo Braca site; the most influential variables were the VPD (vapour pressure deficit) and precipitation of the summer months that had a negative and a positive effect, respectively. The iWUE showed a negative correlation with growth in Campo Braca and a non-significant one in Falode. Water availability was the most influential variable on F. sylvatica growth and physiology. The iWUE increase was mainly driven by atmospheric CO2 concentration, and by decreased precipitation, as a response of the trees to drought. Our results highlight the importance of understanding the hydrological changes due to climate change for forecasting/modelling forest responses. CO2 increase does not compensate for the effect of adverse climate on F. sylvatica in the forests of southern Italy, while local conditions play an important role in determining tree growth.