Using publicly-available average monthly groundwater level data in 478 sub-basins and 30 basins in Iran, we quantify country-wide groundwater depletion in Iran. Natural and anthropogenic elements affecting the dynamics of groundwater storage are taken into account and quantified during the period of 2002-2015. We estimate that the total groundwater depletion in Iran to be ~ 74 km3 during this period with highly localized and variable rates of change at basin and sub-basin scales. The impact of depletion in Iran's groundwater reserves is already manifested by extreme overdrafts in ~ 77% of Iran's land area, a growing soil salinity across the entire country, and increasing frequency and extent of land subsidence in Iran's planes. While meteorological/hydrological droughts act as triggers and intensify the rate of depletion in country-wide groundwater storage, basin-scale groundwater depletions in Iran are mainly caused by extensive human water withdrawals. We warn that continuation of unsustainable groundwater management in Iran can lead to potentially irreversible impacts on land and environment, threatening country's water, food, socio-economic security.