A sloboda (a settlement for people relieved from paying taxes) appeared on the site of modern Kalyazin in the 12th century.[1] Its importance grew significantly with the foundation of the Makaryevsky Monastery on the opposite bank of the Volga in the 15th century.[1] This abbey used to be the most conspicuous landmark of Kalyazin and comprised numerous buildings of historic interest, including a refectory from 1525.[citation needed] The name of the town originates from certain Kolyaga, a land proprietor in the 15th century.[1]

In the 18th century, the area was included into Moscow Governorate.[citation needed] In 1775, Kalyazin was granted town rights[1] and Kalyazinsky Uyezd was established.[citation needed] It was a part of newly established Tver Viceroyalty.[citation needed] In 1796, the Viceroyalty was abolished and transformed into Tver Governorate.[citation needed] Kalyazinsky Uyezd was abolished, but in 1803, it was re-established.[2] On May 30, 1922, Kalyazinsky Uyezd was abolished and merged into Kashinsky Uyezd.[3] On October 3, 1927, Kashinsky Uyezd itself was abolished and split between Bezhetsky and Kimrsky Uyezds.[3]

On August 12, 1929, Tver Governorate was abolished, with its territory transferred to Moscow Oblast.[3] Uyezds were abolished as well, and Kalyazinsky District, with the administrative center in Kalyazin, was established within Kimry Okrug of Moscow Oblast.[3] On July 23, 1930, the okrugs were abolished and the districts were directly subordinated to the oblast.[4] On January 29, 1935, Kalinin Oblast was established, and Kalyazinsky District was transferred to it.[3]

In 1940, the monastery and most of the old town were submerged under water during the construction of the Uglich Hydroelectric Station, which created the Uglich Reservoir. After that, the town was effectively relocated to a new, higher spot.

 The Flooded Belfry is a part of the flooded church and the most eye-catching landmark of Kalyazin

On February 13, 1963, during the abortive Khrushchev's administrative reform, Kalyazinsky District was merged into Kimrsky District, but on March 4, 1964 it was re-established.[3] In July 1990, Kalinin Oblast was renamed Tver Oblast.[5]

On November 19, 2001, a chartered IRS Aero Ilyushin Il-18 airplane crashed in Kalyazin, killing all twenty-seven on board.[6] On August 26, 2010, dozens of Central Asian guest workers were deported from the town after mass clashes with the locals.[7] Their construction site jobs were given to locals instead.[8]