Northern India and its surroundings, home to roughly 600 million people, is probably the most heavily irrigated region in the world. Temporal changes in Earth's gravity field in this region as recorded by the GRACE satellite mission, reveal a steady, large-scale mass loss that we attribute to excessive extraction of groundwater. Combining the GRACE data with hydrological models to remove natural variability, we conclude the region lost groundwater at a rate of 54 ± 9 km3/yr between April, 2002 (the start of the GRACE mission) and June, 2008. This is probably the largest rate of groundwater loss in any comparable-sized region on Earth. Its likely contribution to sea level rise is roughly equivalent to that from melting Alaskan glaciers. This trend, if sustained, will lead to a major water crisis in this region when this non-renewable resource is exhausted.