Mansa district in Malwa region of South-West Punjab has gained significant attention due to elevation in number of patients suffering from diverse diseases especially cancer and consumption of contaminated groundwater could be one of the possible reasons. The present study reports the assessment of 59 groundwater samples from Mansa district by evaluating physicochemical characteristics, potentially toxic element (PTE) contamination and associated health implications followed by analysis of water quality status using various indices. Multivariate statistics were applied for source identification of PTEs in groundwater. The study revealed occurrence of PTEs with mean (μg L⁻¹) dominance order of As (650.8) > U (104.14) > Zn (55.3) > Fe (34.4) > Hg (8.3) > Mn (5.1) > Cu (4.1) > Cr (2.7) > Pb (2.4). One hundred and 71.19% groundwater samples were found to be seriously contaminated with As and U, respectively, and posing high cancer risks to local residents via ingestion. Higher hazard indices of 16.64 and 12.85 for children and adults, respectively, indicated high non-carcinogenic health risks to both population groups but children were observed to be more vulnerable. Correlation analysis showed positive correlations of U with total dissolved solids (TDS), fluoride (F⁻) and total alkalinity (TA). Principal component analysis (PCA) and cluster analysis (CA) revealed the contribution of both geogenic (weathering of rocks) and anthropogenic sources (overuse of agrochemicals in agricultural lands and release of inefficiently treated industrial effluents) for deteriorating the groundwater quality of study area. The study counsels the inhabitants to consume treated groundwater as ingestion route was identified as the primary route of exposure.