[10] The island of Klichen was first mentioned in a letter sent by Grand Duke Algirdas of Lithuania to the Ecumenical Patriarch of Constantinople in 1371.

After the island was pillaged by Novgorod pirates several years later, two of Klichen's surviving inhabitants, Ostashko and Timofey, moved to the mainland, where they founded the villages Ostashkovo and Timofeyevo, respectively.

Local landmarks include the Ascension Church (1689), the Trinity Cathedral (1697), the Monastery of the Sign (1673, 1730s, 1880s), and the mid-18th century Zhitny Cloister.

The town's pleasant architecture and attractive setting by the lake combine to make Ostashkov one of the most popular resorts in Western Russia.

It was the place where the Ostashkov Special Camp of the NKVD was and where roughly 6,300 Polish policemen and prisoners of war were kept before they were executed in Tver.

Approximately 4,300 of their comrades, held in Kozelsk, were around this time executed in Smolensk Oblast at Stalin's order in April and May 1940, in what is now known as the Katyn massacre.

[11] On 1 October 1929, governorates and uyezds were abolished, and Ostashkovsky District with the administrative center in Ostashkov was established.

During World War II, Ostashkov was not occupied by German troops but until 1943 stayed in the immediate vicinity of the front lines.

[11] Soviet flotilla on the lake Seliger was involved in evacuation of Leningrad and Kalinin industrial equipment, military supplies, wounded and refugees.

In the period 1939 to 1941, during the first years of World War II, the monastery at Stolobny Island, about 10 km (6.2 mi) north of Ostashkov, was a prisoner-of-war camp of the Russian secret service NKVD, which held approximately 7,000 Poles who had been taken captive by the Soviet Union as a result of the Molotov–Ribbentrop Pact.

On 25 September 1941 the frontline approached the town, and local authorities were ordered to evacuate all the industrial equipment from Ostashkov to Bely Gorodok.

After the Germans entered the village of Selizharovo, all the barges were dispersed along the river and covered by trees and bushes.

Soviet lake flotilla command faced German bombardments in harsh winter conditions when the barges were blocked by ice.

The new waterways across the Khrestnoye, Seremo and Glubokoye lakes, which were not considered navigable earlier, were used for evacuation of the wounded and shipping the military supplies.

As the Ostashkov tannery was evacuated to Kazakhstan the only industries remaining in the town were: workshop, power plant, mechanized bakery and mill.

There is also regular(on Saturday) steam locomotive train connection with Bologoe(station located on the Moscow - Saint Petersburg railway).