Environmental and cultural changes in the Central Andean region can most successfully be understood through multidisciplinary approaches, combining archaeological and historical research with detailed reconstruction of past climate and vegetation. Here we present a multi-proxy dataset from a small, infilled lake basin in the Cuzco region of Peru that reflects the ecosystem dynamics of both terrestrial and semi-aquatic/aquatic communities. Marcacocha (altitude 3355 m) has a morphology and location that renders it extremely sensitive to environmental change. Organic sediments cored from the centre of the basin have provided a unique insight into how this lake system has responded to local/regional climatic forcings and anthropogenic pressures over the last 4200 years. A series of quasi-periodic, sustained arid episodes have been identified using sedge pollen abundances as a proxy for lake-level variations. Many of these episodes correspond to periods of significant cultural turnover in the independently-dated archaeological record. In particular, data point to the importance of a warm and arid interval that began ~AD 900, which may correspond to the Northern Hemisphere Medieval Warm Period. This interval, which lasted until the end of the 15th century, saw the decline of the Wari Empire (and the Tiwanaku around Lake Titicaca) at ~AD 1100 and allowed the development of the Inca State, the largest Empire ever seen in the New World (~AD 1400-1532). Verifying how these arid climatic periods may have impacted on human societies is difficult, however, given that pre-Spanish Andean cultures failed to develop any form of written record. We therefore present a new method of reconstructing rural socio-economic shifts from the analysis of the frequency of oribatid mite remains. Oribatid mites are soil-dwelling microarthropod detritivores, some of which inhabit areas of grassland pasture. One of the primary controls governing their abundance in such habitats is the level of animal dung present. We propose that past fluctuations in mite remains can be related to the density of domestic animals using the pasture and, by extension, may provide a proxy for broad-scale social and economic change through time. The 6-yr resolution of the Marcacocha record is ideal for testing this hypothesis, by comparing the timing and magnitude of mite fluctuations since the 1530s with a series of well-documented socio-economic shifts in the region that relate to past political and climatic pressures. Results demonstrate remarkable correspondence between the two datasets, providing the confidence to extend the record back a further 3700 years.