Abstract: Given the highly sensitive response of the Qinghai-Xizang Plateau to climate change, studying the impact of long-term climate change on suitable areas of highland barley cultivation on this plateau can offer valuable insights into how plateau agriculture responds to climate change. This, in turn, can facilitate the optimization of the spatial arrangement of highland barley cultivation. In this study, 163 highland barley samples from the Qinghai-Xizang Plateau were used as the study object, the primary environmental factors affecting the distribution of highland barley on the plateau were simulated and predicted using ArcGIS software and the Maximum Entropy Model. In addition, the influence of climate change on the distribution range and spatial pattern of highland barley on the plateau across various historical periods (the Last Inter-glacial Period, the Last Glacial Maximum Period, and the Mid-Holocene Period) and contemporary times (1970—2000) was investigated, and the impact in the future (2021—2100) was simulated under two scenarios (SSP126 and SSP585). The following results were obtained. 1) The most critical environmental factors affecting the distribution of highland barley across the plateau included annual precipitation, annual average temperature, average temperature in the driest quarter, and altitude. In unstable, extremely dry, and cold climates, the suitable areas for highland barley production was mainly determined by elevation. 2) From the Last Inter-glacial Period to the Mid-Holocene Period and then to the present era, the suitable areas for highland barley had gradually expanded to the Hehuang Valley in the northeastern section of the Qinghai-Xizang Plateau, the Western Sichuan Region in the southeastern margin of the plateau, and Yarlung Zangbo River and its two tributaries in the Southern Xizang Valley. In the future, the suitable areas for highland barley will further expand towards the central and northern parts of the plateau, whereas the suitable areas in the southeast will decrease. 3) Under the conditions of SSP126 scenario climate change, the centroid of suitable growth areas for highland barley will move towards high-latitude and high-altitude regions, and the upper suitable limit of altitude will increase by 207 m in the future. By integrating findings from other studies, it can be inferred that the expansion of suitable highland barley-planting areas from the Last Glacial Period to the Holocene Period was influenced by a dual effect, including climate warming and humidification. However, the human settlements on the plateau and the spread of agriculture and animal husbandry also played significant roles in shaping this expansion. From the present to the future, the expansion of potentially suitable areas for highland barley cultivation may be facilitated by an increase in altitude limits caused by climate warming. Conversely, the reduction in these potentially suitable areas may be driven by specific climate change events resulting from temperature fluctuations, ultimately exceeding the optimal temperature range for high barley development.