Quaternary glaciations have significantly impacted the midcontinental North American landscape, leaving behind a proglacial sediment record of glacial lake deposits, glacio-fluvial sand and gravel, and windblown loess. This paper aims to expand upon a previous study using detrital zircon provenance analysis to investigate midcontinental North American loess provenance in relation to the glacial history of the southern Laurentide ice sheet during the middle to late Pleistocene. The study incorporates previously published detrital zircon data from last glacial tills (representing the Huron-Erie Lobe, Lake Michigan Lobe, Green Bay Lobe, Superior Lobe, Des Moines Lobe, and James Lobe), middle to late Pleistocene loess from several sites along the Illinois and Mississippi River valleys, and suspended sediment load inputs from the Missouri River and Arkansas River. A statistical mixing model (DzMix version 2.2) was used to estimate the relative proportions of glacial and nonglacial sources to Wisconsin Episode, Illinois Episode, and pre–Illinois Episode age loess. We show that mixing models that include the modern suspended sediment loads of the Missouri and Arkansas Rivers significantly improve (up to 23% increase in cross-correlation value) the source characterization of Wisconsin Episode (last glacial) and Illinois Episode (penultimate glacial) loess deposits within the Mississippi River drainage basin. These river sources are dominant inputs for certain loess sites (as much as 51%), but their relative contributions are not static across time and space, which has implications for temporal and spatial differences in relative sediment source estimates and glacial and fluvial sediment transport evolution. Specifically, differences in relative sediment proportion estimates among Wisconsin, Illinois, and pre–Illinois Episode loess support previous evidence for the persistence of a Quebec-Labrador ice dome source through multiple glacial cycles, even with the inclusion of river sources in updated mixing models. Illinois and pre–Illinois Episode loess in the southern portion of our study area received ~20% detrital zircon input from sources similar to the present-day Missouri and Arkansas Rivers, suggesting that these river systems were contributing a significant amount of detritus to the lower Mississippi River valley region during the middle Pleistocene.