The first fortification on a high cape located near the confluence of the Buzhok and Southern Bug rivers dates back to the period of Kievan Rus'.
The first stone castle was built here during the time of the Grand Duchy of Lithuania (14th century), when the Koriat's owned the Podolia land.
Since 1731, as a result of his marriage to Countess Maria Zofia Sieniawska, the castle became the property of prince August Aleksander Czartoryski and their descendants as part of the dowry.
In the 18th century the castle lost its important military purpose and turned into one of the provincial residences of the Czartoryski family.
After the second division of the Polish-Lithuanian Commonwealth (1793) and the annexation of the Podolian Voivodeship, Medzhybizh passed to the Russian Empire, but remained the property of the Czartoryski family.
In 1819, prince Adam Jerzy Czartoryski opened a school in the castle for children of the local nobility.
The Palace of the Sieniawski and Czartoryiskyi families was built in the 16th century as a complex of residential, defense and economic buildings.
The current palace in the Renaissance style was built over the previous buildings of the period of the Grand Duchy of Lithuania.
Since the most famous owner of Medzhybizh castle Mikołaj Sieniawski (1489–1569) was a Calvinist, the attic of the newly built palace contains characteristic symbols of Protestantism (stylized communion cups and others).
The church of the 16th–19th centuries was built in 1586 (according to other sources in 1591) as the castle chapel of St. Stanisław in honor of the return of the Sieniawski family to Catholicism.
Medzhybizh castle was entered into the category of "Landmarks and Architecture Monuments" of the State Register of National Cultural Heritage on July 2, 1999 (protection No.
In accordance with the resolution of the Cabinet of Ministers of Ukraine dated 27.12.2001, the State Historical and Cultural Reserve “Mezhybizh” was created.
In April 2022, at the annual international conference in Terezin, Medzhybizh Castle was granted the status of official stop on the European Cultural Route FORTE CULTURA.