The area of the district was populated from prehistory and served as a junction between waterways along the Lovat, the Volga, and the Zapadnaya Dvina.

Numerous archeological monuments were found in the area of the district dating from the 5th millennium BC.

The area was attractive because it gave an easy access to control of the most important waterways, and was a subject of frequent wars.

[10] On 1 October 1929, governorates and uyezds were abolished, and Penovsky District with the administrative center in the settlement of Peno was established.

[12][13] During World War II, a part of the district including Peno was occupied by German troops.

Formerly, timber industry provided the major part of the GDP of the district, however, currently it experiences a deep crisis.

[15] The railway connecting Bologoye with Velikiye Luki crosses the district from northeast to southwest.

In Soblago, a railway branches east and connects with Likhoslavl via Selizharovo, Kuvshinovo, and Torzhok.

A paved road connecting Ostashkov with Zapadnaya Dvina via Peno and Andreapol crosses the district from east to west.

The federal monuments include the wooden Church of the Nativity of Saint John the Baptist (1694) at the village of Shirkovo, the ensemble of the Trinity Church at the village of Otyalovo, the tomb of Liza Chaikina by Nikolai Tomsky in Peno, as well as an archeological monument.