Environmental changes since the late deglaciation are reconstructed from the sediment of Lake Hamoun. Lake Hamoun is located at the border of Iran and Afghanistan where inflowing rivers originate from the drainage basins of SW Hindu Kush Mountains and westernmost Himalaya. The lake has experienced a complex hydrological history during the late Quaternary due to climatic changes. Geochemical, sedimentological, and paleontological proxies as well as geomorphological data were used to investigate environmental changes of the lake. The results demonstrate that since the late glacial, the basin has directly and/or indirectly received its moisture from various climatic systems. During the early Holocene, both the Indian summer monsoon (ISM) and the mid-latitude westerlies (MLW) intensified and consequently the basin received higher precipitation. This interpretation is supported by higher content of total organic matter (mean: 8.2%), finer-grained sediments with low δ18O values (mean: -3.5‰), as well as rich fossil content. Lower organic matter content (< 5%), higher magnetic susceptibility values (5.8–10×10−4 SI unit), and coarser-grained sediments with no shell fragments support the dominance of an arid environment during the early-mid Holocene. The results of stable isotopes suggest weakening of ISM and intensification of MLW during the mid-late Holocene in the study area, when Bronze Age civilizations emerged in the Sistan Basin. In the late Holocene, lake levels experienced more severe fluctuations due to variations in the MLW. Shifts in settlement areas seen in the archaeological record may thus have been a response to climatic changes.