We investigate the distribution of archaeal lipids in a 5.8-m-long sedimentary core recovered from Lake Qinghai to extract regional hydroclimate and temperature signals since the last deglaciation for this important region. The paleohydrology was reconstructed from the relative abundance of thaumarchaeol (%thaum) and the archaeol and caldarchaeol ecometric (ACE) index. The %thaum-inferred lake-level record was extended to deglaciation, showing three periods (11.9–13.0, 14.1–14.7 and 15.1–17.2 cal ka BP) with relatively higher lake levels than those during the early Holocene. The ACE record demonstrates three periods (10.6–11.2, 13.2–13.4 and 17.4–17.6 cal ka BP) of elevated salinity when the lake was shallow. Filtered TEX86 record based on archaeal lipid distributions corresponded to relatively higher lake levels, implying that a certain lake size is required for using the TEX86 paleothermometer. At 1–4 cal ka BP, the reconstructed temperature fluctuated significantly and correlated negatively with inferred lake level, indicating that lake temperature and hydrological change might be coupled during this period. We attribute this co-variance to the importance of summer temperature in controlling evaporation for this arid/semi-arid region. Moreover, our results indicate that archaeal lipids have potential in reconstructing paleoclimate patterns from lacustrine sedimentary cores, but the data should be interpreted with care.