AbstractThe prolonged interplay between orographic and climatic changes creates biogeographic barriers, resulting in the allopatric differentiation of plants in the Himalaya–Hengduan Mountains. Such consequences have led us to investigate the long-term Neogene–Quaternary geo-climatic history of the Eastern Himalaya–Hengduan Mountains. Narrowly distributed populations of Koenigia forrestii were sampled (ten populations, 97 individuals) and analysed for their genetic architecture, including phylogenetic reconstruction (based on plastome and plastid DNA/nuclear regions), molecular dating and demography, in combination with niche dynamics. We estimated that K. forrestii (stem age: 11.39 Mya) diverged into three non-overlapping distributed lineages during the Neogene–Quaternary periods (5.84–2.57 Mya), with Eastern Himalaya (EHa) being the first and most diverse lineage. ‘Isolation by environment’ revealed the existence of genetic structures that were significantly affected by the disparate environment. The presence of demographic events is well supported by the Bayesian skyline plot, indicating recent demographic expansion. Hence, lineage divergence and differentiation were mainly triggered by the heterogeneous environment associated with the biogeographic barriers due to the Tsangpo-Brahmaputra Grand Canyon, Mekong-Salween Divide and local mountain systems. Nevertheless, niche shift and local adaptation are the keys to determining the genetic architecture, demographic dynamics and diversification history of K. forrestii.