The evolution and current distribution of species on the Qinghai-Tibet Plateau have been significantly impacted by historical occurrences, including the uplift of the plateau and the Quaternary climate upheaval. As a remnant species, the plateau pika (Ochotona curzoniae) is a great model for researching historical events. In this study, 302 samples from 42 sample sites were utilized to analyze the impact of historical events on the evolution and distribution pattern of plateau pikas. The genetic diversity, patterns of differentiation, and historical dynamics of the plateau pika were investigated using molecular markers that included four mitochondrial genes (COI, D-loop, Cytb, and 12S rRNA) and three nuclear genes (GHR, IRBP, and RAG1). The results showed that: (1) The genetic diversity of the plateau pika was high in the Tibetan Plateau (Hd = 0.9997, π = 0.01205), and the plateau pika evolved into five lineages that occupied different geographical areas, with lineage 1 (Group 1) in the south of the Yarlung Zangbo River, lineage 2 (Group 2) in the hinterland of the plateau, lineage 3 (Group 3) in the northeastern part of the plateau, lineage 4 (Group 4) in the Hengduan Mountains, and lineage 5 (Group 5) in the eastern part of the plateau. (2) The gene flow among the five lineages was low, and the differentiation level was high (Nm < 0.25; Fst > 0.25), indicating that the geographical barriers between the five lineages, such as the Yarlung Zangbo River, the Qaidam-Ghuong-Guide Basin, and the Lancang River, effectively promoted the population differentiation of the plateau pika. (3) The plateau pika first spread from the Hengduan Mountains to the entire Qinghai-Tibet Plateau and then conducted small-scale migration and dispersal in several refuges across the plateau in response to climate changes during the glacial and interglacial periods. (4) Except for Group 1 and Group 4, all the other populations exhibited a rapid expansion between 0.06 and 0.01 Mya, but the expansion was considerably delayed or halted by the effects of climate change during the last glacial maximum (0.02 Mya). Overall, the plateau pika on the Qinghai-Tibet Plateau exhibits high genetic diversity, and topographic obstacles, including mountains, valleys, and basins, created by the uplift of the plateau and climatic changes since the Quaternary period have played an important role in the differentiation and historical dynamics of the plateau pika population.