In terms of area, this is the largest district in the autonomous okrug. The district is located in a mountainous region, the peaks of which provide the catchment areas for the Anadyr River and its tributaries. The district is home to a large number of indigenous peoples as well as Russians and Ukrainians. Humans have been living in what is now Anadyrsky District for at least five thousand years. Following the foundation of the first Russian-speaking settlements by Semyon Dezhnyov, this territory became the key part of the region in terms of trade, exploration, and administration, which still continues today.
Anadyrsky District is the largest district within Chukotka, with the territory of the district corresponding closely to the basin of the Anadyr River. It covers much of the interior of Chukotka. The eastern border consists of a coastline on the Bering Sea.
The vastness of the district means that natural conditions within it vary considerably, from the mountainous tundra found in the north, to impenetrable woodland in the south, to wind-lashed coast to the east. The district, particularly its eastern part, is dominated by the 800-kilometer (500 mi) long Anadyr River, which forms an estuary known as the Anadyrsky Liman emptying into the Gulf of Anadyr. All of the major inhabited localities on the territory of the district (Anadyr, Ugolnye Kopi, and Shakhtyorsky) are found on the banks of this estuary. The boundary between the estuary and the Gulf of Anadyr is marked by the Russkaya Koshka (where "koshka" is a local term meaning "a spit"). The vast majority of all inhabited localities of any size are to be found either along the Anadyr or one of its tributaries.
The Anadyr Plateau and Pekulneysky mountain range are found in the north and northwest of the district, within which the upper reaches of the Anadyr River drain.
More southerly tributaries of the Anadyr River, such as the Mayn, have their sources in the spurs of the Koryak Mountains in the south of the district. The northeastern-most extent of the taiga is found in the west of the district, on Opalyonnaya Mountain, near the selo of Markovo.