The Mississippi River Basin (MRB) is the 4^th largest watershed in the world, draining 40% of the continental US and the entire American corn and grain belts. 57% of US farmland lies within the MRB, including 80% of all US corn and soybean acreage. This is an agricultural watershed. The Mississippi River is a world class river and ranks among the top ten rivers of the world for length and discharge. Over half of all US grain exports are transported through the Mississippi River as are 40% of the nation’s total exports. What, then, is the condition of the river and the historical water quality of the river’s sub-basins? This presentation will reconstruct the history of agricultural land use changes in the MRB using spatially explicit data mapping techniques and over one hundred years of cropping data from the Census of Agriculture. The results show the specialization of corn and soybean agriculture in the Midwest and Mississippi River valley over the last century. These historical changes in American agriculture and land use practices will be discussed with regard to local water quality parameters and statistically significant relationships between agricultural land uses and subsequent watershed nutrient concentrations will be presented to support the discussion. This analysis and approach is necessary in light of the potential agricultural growth in a biofuel driven market. What are the potential ramifications for water quality in the Mississippi River Basin?