Considerable efforts have been devoted to decipher the late Quaternary moisture and thermal evolution of arid central Asia. However, disparate interpretations still exist concerning different proxies. The spatial and temporal heterogeneities have inhibited a holistic understanding of general patterns and underlying mechanisms. To address these issues, two parallel cores (ONW I, 6.00 m; ONW II, 13.35 m) were retrieved in the Gobi Desert of Mongolia from lake Orog Nuur. Multidisciplinary investigations including geomorphological mapping, radiocarbon dating, sedimentological, palynological and ostracod analyses enabled us to gain a comprehensive dataset for vegetation development and hydrological variability over the last ~45 kyr. Higher lake levels during the Marine Isotope Stage (MIS) 3 and early MIS 2 (~35–~24 kyr) were probably caused by increased precipitation. The sharp transition of Termination I (~11 kyr) is indicated by sedimentological, palynological, and ostracod data. During the late Pleistocene, the lower area of the Orog Nuur catchment was dominated by Artemisia steppe and gradually altered to Chenopodiaceae desert steppe in the Holocene. The early Holocene is also characterized by a relatively humid environment. The humid pulses during the MIS 3 and the early Holocene were also recorded in other archives and are possibly the trait of a larger scale phenomenon in arid central Asia. Four major harsh climatic periods were documented in the core at ~43 kyr, ~36 kyr, during the global Last Glacial Maximum, and the Younger Dryas as playa phases. Reduced westerlies' moisture transport and a retreated East Asian Summer Monsoon influence probably caused those dry phases in the Gobi Desert of Mongolia.