The biggest tributaries of the Sukhona within the district are the Lezha (right), the Dvinitsa (left), the Shuya (right), and the Ikhalitsa (right).

The district thus lies on the divide between the basins of the Northern Dvina and Volga Rivers, or between the Arctic Ocean and the Caspian Sea.

[10] The biggest one is the Bolshaya Chist Swamp located between the valleys of the Sukhona and the Tolshma and shared by Totemsky and Mezhdurechensky Districts and Kostroma Oblast.

The principal direction of the colonization was along the Sukhona, which at the time was the main waterway connecting central Russia with the White Sea.

The selo of Shuyskoye was first mentioned in 1555 as Shuysky Nizovets and achieved prominence in the 17th century as a settlement of shipbuilders, delivering ships mainly to Vologda.

In 1370, Avnezhsky Monastery was established on the bank of the Sukhona at the mouth of the Avnega River.

[10][12] In the course of the administrative reform carried out in 1708 by Peter the Great, the area was included into Archangelgorod Governorate.

The viceroyalty was abolished in 1796, and the part of it which included the area of what is now Mezhdurechensky District was made into Vologda Governorate.

Instead, Shuysky District with the administrative center in the selo of Shuyskoye was established as a part of Vologda Okrug.

On July 15, 1929, Tolshmensky District with the administrative center in the selo of Krasnoye[13] was also established.