This study focuses on the early human occupation of the arctic part of the West Siberian Plain and introduces the finds at the Paleolithic site Kushevat (Shuryshkarsky District, Yamal-Nenets Autonomous Okrug), discovered in 2020. Geological and geomorphological characteristics of the Lower Ob region are provided, the chronology of the key Middle and Late Neopleistocene sequences is assessed, and criteria underlying the search for Paleolithic sites in the area are outlined. We describe the discovery and excavations at Kushevat, its stratigraphy and its faunal remains. On the basis of correlation with neighboring key Late Neopleistocene sections with a representative series of absolute dates, the age of the site is estimated at cal 50–35 ka BP. Results of a traceological study of a possibly human-modified reindeer antler are provided. Findings at Kushevat and the available information on the early peopling of northern Eurasia suggest that the boundary of the inhabited part of that region must be shifted ~200 km to the north. The Ob, therefore, is one of the last major Siberian rivers where traces of the Early Upper Paleolithic culture have been found. The discovery of a stratified site in its lower stretch is a milestone in the Paleolithic studies in the region. A large area over which faunal remains are distributed, and the presence of lithics among the surface finds, suggest that Kushevat is a highly prospective site for future archaeological studies of the early stages in the human peopling of the region.