Water is an essential component for the survival of humans and animals. Due to industrialization, water is being contaminated with varying polluting agents, arsenic (As) contamination is one of them. An exclusive study was carried out for the determination of As in groundwater of Larkana city using microwave-assisted digestion followed by atomic absorption spectrometry (AAS). For that purpose, a total of 110 groundwater samples were collected from 10 union councils (UCs) of the city based on global position system (GPS) method. Results revealed that maximum concentration of As was found 17.0 μg/L in UC-6, while in UC-1, UC-2 and UC-10 the concentration of As was found within the permissible limits of WHO. The minimum and maximum mean concentration of As was found 3.59 μg/L and 6.78 μg/L, respectively. Out of 110 ground water samples of Larkana city, 13 samples were found above the permissible limits (~12% of total samples). Hence, water can be used for drinking purpose with caution.