The study aims to evaluate the overall water quality (WQ) by utilizing the Canadian Council of Ministers of the Environment water quality index (CCME-WQI), Pollution Load Index (PLI), Water Pollution Index (WPI), Enrichment Factor (EF), Geo-accumulation Index (GI/Igeo), Modified degree of contamination (MDC/mCd), Heavy Metal Pollution Index (HPI), Contamination index (CI/Cd), geographic information system (GIS), and map overlay approaches in Mahanadi River Basin, Odisha, India. Notably, twenty surface water samples collected during the monsoon season are analyzed, and the results are compared with the guideline value, as per WHO guidelines for drinking and domestic purposes. Further, the water samples’ ion abundance is in the following order: of anions, Cl− > SO42− > NO3− > F− and cations, Fe2+ > B+. Moreover, the model namely, CCME WQ characterization for the assigned use, has been presented to examine and note the importance of the elements on the river WQ evaluation, and it demonstrates that the maximum surface water samples (n = 14, 73.68%), fits under good category and finally, are safe to consume without the need for regular medical attention. Further, it is apparent from PLI values that water belongs to the category of no pollution to polluted zone with PLI values ranging from 0.23 to 4. In the case of WPI, the river water possesses a value ranging from 0.29 to 15, falling under the very pure to highly impure category. Besides, EF indicates the areas where surface water was unsuitable as a drinking source were around 31.58%, containing 6 locations. Such results computed, fall within a value between 0.5 and 46, indicating deficiency to extremely high enrichment zone. The analysis of CI was employed to measure the total pollution load on water bodies, and the results show that the water quality falls into the low to high range. Hence, the index reveals that around 36.84%, i.e., 7 sites are unfit for consumption unless they have undergone adequate cleaning and treatment. The index GI, classified the river water, as uncontaminated/moderate for drinking at ten stations (52.63%) and finally, comes under the polluted category of around 47.37% at nine survey sites, thus elaborating the river water as unsuitable for drinking purposes in the entire river. The categories of WQ evaluated by MDC values of the major part of the study area fall under low to moderate degree of contamination (57.89%) during the whole study period. Moreover, the method, HPI demonstrates the categorization of the river water, that reflects under poor and severely contaminated class at the three sites (15.80%), signaling that immediate management of the water is required since it is unfit for human consumption, drinking, or the healthy survival of aquatic life. A significant amount of anthropogenic and industrial waste is suggested by a high concentration of several parameters that are present everywhere, which raises WQ values. From the study, it can be claimed that some places have extremely low water quality, and that the water should be properly treated before usage.