Arsenic-contaminated aquifers are currently estimated to affect ~150 million people around the world. However, the full extent of the problem remains elusive. This is also the case in Pakistan, where previous studies focused on isolated areas. Using a new data set of nearly 1200 groundwater quality samples throughout Pakistan, we have created state-of-the-art hazard and risk maps of arsenic-contaminated groundwater for thresholds of 10 and 50 μg/liter. Logistic regression analysis was used with 1000 iterations, where surface slope, geology, and soil parameters were major predictor variables. The hazard model indicates that much of the Indus Plain is likely to have elevated arsenic concentrations, although the rest of the country is mostly safe. Unlike other arsenic-contaminated areas of Asia, the arsenic release process in the arid Indus Plain appears to be dominated by elevated-pH dissolution, resulting from alkaline topsoil and extensive irrigation of unconfined aquifers, although pockets of reductive dissolution are also present. We estimate that approximately 50 million to 60 million people use groundwater within the area at risk, with hot spots around Lahore and Hyderabad. This number is alarmingly high and demonstrates the urgent need for verification and testing of all drinking water wells in the Indus Plain, followed by appropriate mitigation measures.