Anthropogenic activities such as wastewater discharge by industries, mining, and electricity generation cause an increase in the concentration of some toxic heavy metals in the river environment. In addition, agricultural activities in the vicinity of the river environment may cause the enrichment of heavy metals. In the present study, heavy metal concentrations of Pb, As, Hg, Ni, Zn, Cu, Cr, and Mn along the Ponnai river, Tamil Nadu are considered to assess the role of industrial and agricultural activities. Emanating from the Paradarami hill ranges, the Ponnai River is seasonal and remains generally dry and sandy throughout the year, and does not contribute much to sustained irrigation. However, the river area has the benefit of receiving rainfall during both southwest and northeast monsoon periods. Statistical approach to assess the distribution of heavy metals by means of quantitative pollution parameters like the geo-accumulation index (Igeo), contamination factor (CF), and pollution load index (PLI) indicate the sand samples are not polluted by measured heavy metals and hence there is no influence of anthropogenic activities are in the study area. In this analysis, PLI accounted for 25.34% of the total variance and was positive with loadings of As, Cu, Zn, Cr, Ni, and Mn; PC2 accounted for 11.25% of the total variance and was significant loadings with Cu, Cr, and Ni. These results suggest that the heavy metals represented by PLI were predominantly derived from natural sources, except for As and Cr.