In 1993 and 2019, the Mississippi River Basin (MRB) experienced unprecedentedly persistent extreme precipitation events that resulted in a notable number of catastrophic flooding episodes. These floods caused disruption to almost every area of human endeavor and brought widespread damage to agricultural lands, homes, businesses, and infrastructure. These large flood events were associated with extreme rainfall events over an extended period and encompassed a number of U.S. states. We conducted two case studies: the MRB flooding events of 1993 and 2019. For each case study, we conducted a literature review and examined the sequence of extreme precipitation events and the evolution of flooding. We identified synoptic-scale atmospheric patterns by examining meteorological variables such as precipitation, geopotenial heights and precipitable water. The global teleconnection patterns that were conducive and precursors to the heavy precipitation were investigated as well through climate indices such as Arctic oscillation, North Atlantic Oscillation, Pacific-North American pattern, and El Niño Oscillation (through Southern Oscillation Index and Sea Surface Temperature Anomalies). We also verified the weather maps based on actual observations during the occurrence of extreme precipitation events. Lastly, we identified the impacts of these extreme precipitation events on biotic communities. Our project has provided a foundation to identify risks and impacts of extreme precipitation on the specific aquatic species, wildlife, and agroecosystems supported by the rivers and streams of the MRB. We consider our research as an early step to understand the impacts of climate change on the greater MRB. The identification in our case studies of synoptic-scale atmospheric patterns and global teleconnection patterns that are conducive to heavy precipitation events within the MRB will help identify what patterns to examine in the future for changes in amount, frequency, extent, and timing as a result of climate change.