We present information gleaned from 10 years of data collected by the water quality component of the Upper Mississippi River Restoration Environmental Management Program’s Long Term Resource Monitoring Program (LTRMP) from Pool 26 of the Upper Mississippi River System (UMRS). The Pool 26 reach of the UMRS includes the confluence with the Illinois River, and the confluence with the Missouri River just downstream of Mel Price Locks and Dam. The surrounding communities in both Illinois and Missouri benefit greatly from the natural resources provided by these rivers. We estimate that annual expenditures are $84 and $55 million for fishing and hunting, respectively, in the region surrounding Pool 26 based on license sales and state expenditure data from the U.S. Fish and Wildlife Service. Additionally, there is a commercial fishery active in Pool 26, recreational boating, and the UMRS provides drinking water for many municipalities in this region. Finally, the Upper Mississippi River System is a major transportation system, and Pool 26 receives the greatest amount of barge traffic for any river reach in the UMRS. The LTRMP began collecting data in 1988, but the first years of the program were experimental. Currently followed monitoring protocols for water quality and fish monitoring were adopted in 1993; however, a major flood event in that year prevented full data collection for that year. Data from the LTRMP water quality component demonstrate that Pool 26 is a highly productive river reach. Long-term averages of chorophyll-a, total phosphorous, total nitrogen, and total inorganic solids are comparable to levels in eutrophic to highly eutrophic lakes. The average current velocity in the main channel of the Mississippi River in Pool 26 ranges from 0.364–0.414 m/sec. during the summer and fall. Even during the lowest discharge levels in a year, the reach has a residence time no longer than 2.7 days. Discharge was significantly related to many water quality parameters, including Secchi depth, turbidity, total suspended solids, total nitrogen, nitrate-nitrite, and total phosphorus. We observed a significant linear increase in mean water temperature in the main channel from 1994 to 2004. When these data were analyzed by season, positive linear trends were found during the spring (0.515°C per year) and fall (0.646°C per year). Continued monitoring is necessary to determine if these observations represent short term fluctuations or long-term trends and to detect any related effects on this river reach.