Several meltwater floods initiated by the Laurentide Ice Sheet (LIS) drained to the Gulf of Mexico (GOM) through the Mississippi River during the last deglaciation (10–21 cal ka [calibrated kiloannum]). Such floods have been efficiently captured in the geochemical record of the Jumbo Piston Core 26 (JPC-26) from the northwestern GOM as distinct peaks in the content distribution of Si, Al, and Fe due to their common occurrence throughout North America. On the other hand, peaks in the content distribution of Ti, K, Zr, and V adequately describe the sediment source of each flooding event due to their clustered areal distribution in North America. The presence of three distinct peaks in the distribution of Si, Al, and Fe at 8.5, 5.2–7.6, and 2.9–3.5 cal ka indicates that events of enhanced Mississippi River discharge (EMRD) occurred during the Holocene as well. The geochemical signature of these flooding events suggests that their origin and sediment source is variable, depending on the retreating state of the LIS and the prevailing precipitation patterns in North America during these time periods. A comparison of the 8.5 and 2.9–3.5 cal ka EMRD events with the oxygen isotope and gas (CH4) records of the Greenland Ice Sheet Project 2 (GISP-2) ice core denotes that these events might be linked to short global warming episodes associated with periods of increased solar irradiance. The 5.2–7.6 cal ka EMRD event is associated with the Holocene Thermal Maximum, which resulted in the intensification of the North American monsoonal circulation.