Karst aquifers in semi-arid regions, like Querenca-Silves (Portugal), are particularly vulnerable to climate variability. For the first time in this region, the temporal structure of a groundwater-level time series (1985–2010) was explored using the continuous wavelet transform. The investigation focused on a set of four piezometers, two at each side of the S. Marcos-Quarteira fault, to demonstrate how each of the two sectors of the aquifer respond to climate-induced patterns. Singular spectral analysis applied to an extended set of piezometers enabled identification of several quasi-periodic modes of variability, with periods of 6.5, 4.3, 3.2 and 2.6 years, which can be explained by low-frequency climate patterns. The geologic forcing accounts for ~15 % of the differential variability between the eastern and western sectors of the aquifer. The western sector displays spatially homogenous piezometric variations, large memory effects and low-pass filtering characteristics, which are consistent with relatively large and uniform values of water storage capacity and transmissivity properties. In this sector, the 6.5-year mode of variability accounts for ~70 % of the total variance of the groundwater levels. The eastern sector shows larger spatial and temporal heterogeneity, is more reactive to short-term variations, and is less influenced by the low-frequency components related to climate patterns.