The river Ganges is regarded as one of the most holy and sacred rivers of the world from time immemorial. The evaluation of river water quality is a critical element in the assessment of water resources. The quality/potability of water that is consumed defines the base line of protection against many diseases and infections. The present study aimed to calculate Water Quality Index (WQI) by the analysis of sixteen physico-chemical parameters on the basis of River Ganga index of Ved Prakash, weighted arithmetic index and WQI by National sanitation foundation (NSF) to assess the suitability of water for drinking, irrigation purposes and other human uses. These three water quality indices have been used to assess variation in the quality of the River Ganga at monitored locations over an 11-year period. Application of three different indexes to assess the water quality over a period of 11 years shows minor variations in water quality. Index values as per River Ganga Index by Ved Prakash et al. from 2000 to 2010 ranged between medium to good, Index values as per NSF Index for years 2000–2010 indicate good water quality, while Index values as per the weighted arithmetic index method for the study period indicate poor water quality.