The Mississippi Valley Loess Plains is a narrow region stretching north-south along the Mississippi river, however, it is not within the floodplain of the river itself, but directly east of it. In the northernmost portion of this ecoregion, it is somewhat narrower that those areas to the south. This region is named for and characterized by Loess, a fine sediment that has accumulated from wind-blown dust.

The topography here is more hilly and irregular than that of the Mississippi Alluvial Plain Ecoregion that is closer to the river. The soils in the Loess plain are deep, fine-textured, and easily eroded. The topography is steepest in the west, and tends to become flatter to the east.

It consists primarily of irregular plains, some gently rolling hills, and near the Mississippi River, bluffs. Thick loess is one of the distinguishing characteristics. The bluff hills in the western portion contain soils that are deep, steep, silty, and erosive. Flatter topography is found to the east, and streams tend to have less gradient and more silty substrates than in the Southeastern Plains ecoregion (65).

To the east, upland forests dominated by oak, hickory, and both loblolly and shortleaf pine, and to the west on bluffs some mixed and southern mesophytic forests, were the dominant natural vegetation. Agriculture is now the typical land cover in the Kentucky and Tennessee portion of the region, while in Mississippi there is a mosaic of forest and cropland.