The US EPA Environmental Monitoring and Assessment Program on Great River ecosystems collected water from 447 sites in the Upper Mississippi, Missouri and Ohio River basin over a three year period (2004-2006).   The method of least squares to fit general linear models (GLM) and canonical discriminant analysis was used to compare general water chemistry between the three rivers and five river reaches: impounded and unimpounded reaches of the Upper Mississippi River, the upper and lower reaches of the Missouri River, and the entire Ohio River.   The Ohio and Missouri rivers were most dissimilar with water clarity being the discriminating factor.  The upper and lower reaches of the Missouri River were most similar to each other with GSD of 41.68 and most dissimilar to the impounded Mississippi reach GSD 272.41 and 278.16 respectively. GLM indicates both impounded and unimpounded Mississippi reaches were nutrient rich in comparison with the other river reaches.  The Missouri river reaches have the highest cation (Ca, Mg, Na, K), silica, and sulfate concentrations and were the most turbid.  The Ohio River had the highest Cl concentrations and the lowest pH.  A regression analysis indicates a strong landscape influence on water chemistry.