Arsenic (As) is one of the most toxic metalloids for humans. Above permissible levels of As cause severe health implications. Contaminated drinking water and food items may be the leading sources of As exposure to people all around the world. The current study assessed the levels of As in drinking water, vegetables, irrigation water, agricultural soils, and the human population (adult women and men) of rural and peri-urban areas of Multan (Pakistan). For a comparison between peri-urban (exposed site) and rural areas (control site), we sampled irrigation water, vegetables and vegetable-grown soils, drinking water, and human blood. In all sample types, As concentration was significantly higher at exposed site than at control site. Alarmingly, As concentration in drinking groundwater (34 µg As L-1) of exposed site was 3.4-folds higher than the permissible limit (set by WHO). Among the studied vegetables, the cumulative daily dietary intake of As was recorded maximum by the consumption of okra (474 ng d-1 on exposed site) and minimum by long melon (1 ng d-1 on control site). However, As intake via drinking water was estimated to contribute ≥ 98% of total As intake at both sites. Hence, the health risks associated with drinking As-contaminated groundwater were recorded much higher than the health risks associated with the consumption of As-contaminated vegetables. Blood As levels in most of the subjects at exposed site exceeded the safe limit of 12 µg L-1. Conclusively, the findings of the current study indicated that drinking contaminated groundwater may be the major cause of As-associated health risks in the region.