Annual mean spring discharge (ASD) is an important water supply source, essential for ecological systems and societies dependent on groundwater resources. Influenced by both regional and local climate fluctuations, the inter-annual variability of ASD represents a climate memory signal, significantly affected when the drought pattern manifests itself in changing climatic regimes. Gaining a better historical perspective on ASD changes requires extended time-series of discharge data and relevant climate drivers. Here, using a parsimonious model, we present a continuous (modelled) time-series of annual ASD for the karst spring of Caposele, in the Cervialto Massif of southern Italy, which is hitherto the longest (1601–2020 CE) such time-series for the entire Mediterranean region. The model was designed to capture the importance of large-scale seasonal (spring, autumn and winter) precipitation (hydro-meteorological factor), and flood and drought indices (climatological factor), and to be consistent with a sample (1920–2020 CE) of actual data. We show a limited overall sensitivity of ASD to climate variability, with a mean of 4.21 m3 s−1 and a drop from ∼1759 CE. With a mean value of ∼3.60 m3 s−1 after ∼1987 CE, ASD has revealed a substantial descending trend—possibly a fingerprint of recent warming—with a depletion of regional water reservoirs. These results highlight the need to strengthen the capacity of groundwater resources in the face of changing, and possibly enhanced, drought patterns in the Mediterranean region.