This paper reviews evidence of middle Holocene environments, geology, and archaeology in the Southern Plains of the United States. Paleoenvironmental review of data including pollen, vertebrates, mollusks, and stable isotopes indicate drier climates prevailed in this region during the middle Holocene than in the early Holocene or the late Holocene. This climatic record is registered in different patterns of alluvial sedimentology and pedology across the region and among different drainage basins. Middle Holocene eolian deposits are documented in some localities from the Southern High Plains to the eastern plains margins. Reduced biomass and reduced surface water availability appear to have forced demographic and economic responses by middle Holocene populations in this region. However, deep burial of archaeological sites under flood plains as well as a paucity of geoarchaeological investigations constrain clear reconstruction of adaptive changes during this period.