The Kolyma region is historically famous for the unique finds of large Pleistocene fauna, yet, until very recently, absent of the time-corresponding occupation sites. Quaternary geology and palaeontology investigations (2013–2019) in the middle reaches of the Kolyma River (NE Yakutia) have delivered new evidence on the Last Glacial (MIS 4–2) to Early Holocene sub-arctic ecosystems and the past landscape dynamics retrieved from the fossiliferous bodies exposed from thawed grounds. The palaeoecology multi-proxies from the MIS 3 (55–24 ka) cryolithic formations document riparian, larch-dominated northern forests and open parklands with backwater channels, marshlands and lakes. The abundant skeletal remains of Pleistocene ungulates and carnivores, as well as relic flora point to long-term biomass-rich interstadial ecosystems and favourable Palaeolithic occupation habitats. Utilized animal bones, worked mammoth ivory and stone tools show the presence of pre-modern humans in the northeast Russian Arctic >45 000 years ago. Flaked mammoth tusks suggest persistence of settlement during the Last Glacial Maximum in xeric and extremely cold (sub)arctic tundra. The postglacial climate shifts triggered major environmental and hydrological transformations. The final Pleistocene/Early Holocene warming brought restructuring of the Last Ice Age landscape and vanishing of the periglacial tundra-steppe replaced by the present-day larch-dominated Siberian taiga. The mid-Last Glacial human ecology records from the geographical limits of northeast Siberia have fundamental relevance for the reconstructions of the time trajectories and the natural conditions of peopling of Beringia.