Due to global trends in climate and human activity, groundwater is becoming increasingly more important as a water source. Alongside the effects of climate change and anthropogenic factors, natural climate cycles have considerable impacts on the hydrologic cycle. In particular, they can affect groundwater recharge. However, to date only a small number of studies have sought to gauge these impacts at the global scale and to consider their implications in terms of management and policy decisions. In this paper we look at how global climatic oscillations cycles, like El Niño–Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO) and the Atlantic Multi-decadal Oscillation (AMO), affect total water storage and groundwater storage in several large aquifers (area > 100 000 km²) located in varying climatic regions of the world. To evaluate the impact of inter-annual and multi-decadal climate variability on groundwater resources, we look at time series of oceanic indices and compare them to total water storage estimates made from two approaches. The first one is made through the analysis of data from the Gravity Recovery and Climate Experiment (GRACE), which provides information from 2002 to 2017. The second is through a climate-driven model which comprises of two-variables, precipitation and evapotranspiration, that reconstructs past water storage changes from 1980 to 2017. Observed groundwater levels are used to validate these estimates and adapt the methods where possible. Results are expected to show that rainfall patterns connected with the ENSO are the main driver of changes in inter-annual groundwater storage, whereas decadal to multi-decadal variability is believed to be significantly affected by AMO. The combined effect of ENSO and AMO could trigger significant changes in recharge to the aquifers and groundwater storage. These results are aimed at helping to address the threat of water scarcity and the effects of climate variability and change, indicating where more detailed local studies are necessary, and further supply scientific information to support the development of long-term groundwater management strategies of large (in some cases transboundary) aquifers. This study is a contribution to the UNESCO-IHP Groundwater and Climate Change programme (GRAPHIC).