The dried-up lake bed of Lop Nur is a well-known example of environmental change in arid Central Asia (ACA) and witnessed the rise and fall of a major Silk Road civilization. However, a lack of interdisciplinary analyses, quantitative climate data together with inadequate characterization of the desert vegetation has hindered a comprehensive understanding of past vegetation and environmental changes in the region. Here we perform a high-resolution analysis of pollen, grain size, stable carbon and nitrogen isotopes from a 617-cm sediment core from Lop Nur to reconstruct vegetational and environmental changes between ∼23.3 to 7.2 cal kyr BP and understand their potential drivers. Results show that variations in solar activity and westerlies drove water circulation in the region, triggering an alternateon between temperate shrubby desert and temperate semi-shrubby/dwarf semi-shrubby desert, accompanied by the fluctuations in lake level fed by alpine meltwater. Lake organic matter was mainly derived from aquatic vascular plants and phytoplankton in the latest Pleistocene (∼23.3–11.6 cal kyr BP), but shifted to a greater diversity of sources (soil, C₃ terrestrial plants, aquatic vascular plants and phytoplankton) in the early to middle Holocene (11.6–7.2 cal kyr BP), while the nitrogen levels in the lake sediment were mainly controlled by soil erosion, and only marginally influenced by atmospheric nitrogen deposition. These findings provide a past analog for the prediction of future environmental change and ecosystem sustainable development in ACA under the scenario of global change.