[5] The area was originally populated by speakers of Uralic languages and then colonized by the Novgorod Republic.

The area was at the time located on one of the main ways from central Russia to the Pechora River basin and to the Ural Mountains.

[12] In the course of the administrative reform carried out in 1708 by Peter the Great, the area was included into Archangelgorod Governorate.

A major part of the district belongs to the basins of the Mezen River (with the main tributaries the Pyoza and the Kimzha) and the Kuloy River (with the Nemnyuga and the Soyana), which both end up in the Mezen Bay of the White Sea.

The district also includes Morzhovets Island which separates the Mezen Bay from the entrance of the White Sea.

The part of the district located east of the Mezen is essentially unpopulated, with the exceptions of the right bank of the river and of several villages in the valley of the Pyoza.

[3] The following selsoviets have been established (the administrative centers are given in parentheses):[3][14] As a municipal division, the district is divided into two urban settlements and twelve rural settlements (the administrative centers are given in parentheses):[7] The northern part of the district is included into border security zone, intended to protect the borders of Russia from unwanted activity.

In order to visit the zone, a permit issued by the local FSB department is required.

The Mezen horses are rather small but suitable for difficult work and easily survive cold winters.

During winter, temporary roads (zimniks) are built in snow; in summer, air transport is the only means for passenger connections to Arkhangelsk and the rest of the world.

The district contains two objects classified as cultural and historical heritage by Russian Federal law, and additionally a number of objects classified as cultural and historical heritage of local importance.

The objects under local protection are wooden churches, chapels, windmills, peasant and merchant houses.