Paleosols interbedded with pyroclastic deposits have been proven to be an important paleoenvironmental proxy for the late Quaternary in Central Mexico. We studied a key upland section and several profiles on the slopes and lowlands of the Tlaxcala Block, assuming that the topographic variability of the soil-sedimentary mantle contains the complete record of the landscape history. The upland section included three paleosols separated by tepetates (compact volcanic pedosediments) and reflected a general trend of environmental evolution during the last 40 ka. Particle-size distribution, bulk chemical composition, magnetic characteristics, computed tomography, and micromorphological observations demonstrated a strong seasonality of paleoclimate at the end of MIS3, followed by cool wet conditions during the last glacial maximum, subsequent warming at the beginning of the Holocene, and drying during the last 3 ka. It was shown that tepetates had well-developed pedogenetic features that contribute to the paleosol record. The studied slope and lowland profiles reflected the main phases of geomorphic activity in the terminal Pleistocene and the early Holocene. These phases are linked to paleoclimate fluctuations in Central Mexico at the end of the last glaciation.