The present study was conducted on the river Yamuna, which passes through Delhi-NCR from Baghpat to Chhainssa, a distance of about 125 km, at six sampling locations to evaluate the concentrations of heavy metals in surface water using heavy metal pollution index (HPI) approach. The river serves both urban-industrial and rural areas in the study area; hence, domestic, industrial, and agricultural wastes are being contributed greatly in the contamination of river water. The Yamuna River is one of the major tributaries of the river Ganga originated in the Himalayas and is flowing through a varied geological terrain. Metals such as iron (Fe), copper (Cu), cobalt (Co), zinc (Zn), lead (Pb), cyanide (CN), nickel (Ni), and chromium (Cr) in selected sites of Yamuna River water were determined by using atomic absorption spectrophotometer. The concentrations of Fe, Cu, Co, Zn, Pb, CN, Ni, and Cr in the river water were found to be in the range of 40-190, 50-120, 4-66, 840-1800, 2-40, 100-600, 88-253, and 35-52 μg/L, respectively. The results show that the maximum heavy metal content was found at sampling site S3 (Nizamuddin) followed by S6 (Chhainssa), S4 (Okhla), S1 (Baghpat), S5 (Manjhawali), and S2 (Pachahira). The heavy metal data was integrated in GIS environment for preparing spatial distribution maps of sampling sites. A scatter plot matrix was created to assess the pattern and interrelationships between heavy metals. The average concentration of heavy metals was recorded high, often exceeding the permissible limits for drinking of surface water prescribed by the Bureau of Indian Standards (BIS) and World Health Organization (WHO). Based on HPI (varies from 98.2 to 555.1), about 85% of the river water was classified as highly polluted; hence, it is not recommended for drinking. Overall, significant variations were observed in concentrations of heavy metals from one location to the other which may be because of toxic industrial effluents and domestic sewage wastes being added to the river water by various anthropogenic activities in the study area. The present work highlights the pollution load of heavy metals in the river Yamuna and also advocates an urgent attention towards minimizing the health risk of people residing not only along the river banks and surrounding regions but also for city population.