Arsenic (As) contamination in drinking groundwater is a common environmental problem in Pakistan. Therefore, sixty-one groundwater samples were collected from various groundwater sources in District Sanghar, Sindh province, Pakistan, to understand the geochemical behavior of elevated As in groundwater. Statistical summary showed the cations and anions abundance in decreasing order of Na+ > Ca2+ > Mg2+ > K+, and HCO3− > Cl− > SO42− > NO3−. Arsenic was found with low to high concentration levels ranging from 5 µg to 25 µg/L with a mean value of 12.9 µg/L. A major water type of groundwater samples was mixed with NaCl and CaHCO3 type, interpreting the hydrochemical behavior of rock–water interaction. Principal component analysis (PCA) showed the mixed anthropogenic and natural sources of contamination in the study area. Moreover, rock weathering and exchange of ions controlled the hydrochemistry. Chloro-alkaline indices revealed the dominance of the reverse ion exchange mechanism in the region. The entropy water quality index (EWQI) exposed that 17 samples represent poor water, and 11 samples are not suitable for drinking.