The long term history of terrigenous flux to the Gulf of Mexico via the Mississippi River is hardly known. We here present geochemical and sedimentological data to approximate the varying Mississippi River sediment influx into the northeastern Gulf of Mexico (GoM) over the last six glacial-interglacial cycles (MIS 1 to 14). Our study is based on the IMAGES sediment core MD02-2576 that was recovered from the DeSoto Canyon and is located ~ 200 km south to the recent Mississippi River delta and ~ 150 km east of the recent coastline of Florida. Concentrations of siliciclastic elements in bulk sediment samples were estimated from XRF scanning and calibrated by single bulk XRF-analyses. Elemental ratios of the sedimentary record correspond to ratios from the Mississippi River catchment rather than to the core close Alabama and Mobile River catchments. The siliciclastic major element potassium (K) with enhanced surface concentrations in the northwestern Mississippi River catchment shows varying occurrence downcore and here serves as a proxy for Mississippi River sediment discharge variability. Changes in sedimentation rate and magnetic susceptibility further support the variations in Mississippi River influx. Our data were compared with Mississippi River terrestrial archives in the form of loess and terrace deposits that back up our interpretations of enhanced glacial phase Mississippi River influx triggered by strengthened fluvial river runoff and changing fluvial and ice sheet dynamics. Mississippi River influx was at a maximum during glacial MIS 2/3, MIS 8 and MIS 10. Late glacial MIS 6 deviates from this pattern being a period of reduced Mississippi River influx at the core location, probably due to a westward shift of the Mississippi River delta.