During the last deglaciation, the decaying Laurentide Ice Sheet (LIS) delivered huge volumes of meltwater toward the Gulf of Mexico. The present investigation of clay mineralogy and grain-size characteristics of terrigenous sediments deposited in the Orca Basin (Gulf of Mexico) offers a unique opportunity to link the marine record of these meltwater floods with the reconstructed continental glacial history and the modeled drainage patterns. Five peculiar sedimentary levels, characterized by high smectite content and low CaCO3 content, were identified and occurred simultaneously with major meltwater floods. According to recently published clay mineral distribution maps for North America, these results help to pinpoint the southwestern margin of the LIS as a main contributor to most of the meltwater discharges. In addition, the peculiar mineralogical composition (illite and chlorite-rich) of the sediments characterizing the meltwater episode associated with Heinrich event 1 suggests a provenance from the Great Lakes area, supporting the interpretation of destabilization of the LIS southeastern margin during this event. Decreased terrigenous contribution associated with changing provenance of sediments after 12.9 cal ka BP suggests strong modifications of the continental hydrography in relation to Lake Agassiz history and changes in the morphology of Mississippi delta due to rising sea level.