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With over 200 pools, lakes and rivers supporting over 70 species of endemic flora and fauna, the Cuatrocienegas Basin (CCB), Coahuila, NE Mexico, is an extremely important area for conservation studies. However, the palaeoenvironment of this unique area has been relatively neglected. Here, pollen data are presented alongside U-series dating and C-14 AMS dating techniques from a 15-m sediment core taken from Poza Tierra Blanca in the CCB. These data suggest the CCB contains palaeoenvironmental information spanning at least the late Pleistocene (84.5 ka BP) to the present and has undergone extensive environmental change, possibly controlled by stadial-interstadial cycles. The CCB is currently functioning as a hydrologically closed system, established around 4 ka BP synchronously with regional drying of the Chihuahuan Desert. Pollen data suggest similar closed hydrology conditions from 33 to 23.13 ka BP - before the onset of full glacial conditions at the LGM. Hydrologically open system characteristics with a dominance of wetter, winter monsoon climate punctuate the long-term record. The wetter conditions observed in these units appear to have facilitated the downslope movement of montane taxa and the expansion of wetland taxa. These data illustrate that novel vegetation assemblages are not just products of deglaciation but represent the interaction of the individualistic response of taxa with the unique climate spaces formed by millennial-scale variability during both glacial and interglacial times.