Jews began to settle in Horodenka in the 16th century. After the city of Horodenka was granted the Magdeburg right, the Jewish community grew significantly. In 1743, Mykola Potocki granted the Jews of Horodenka the privilege of trade and handicrafts, and a place was allocated for the community for the construction of a cemetery and a synagogue. In the 18th century, a prominent figure associated with the Horodenka Synagogue was the student Bal-Shem-Tova Nachman (who died in 1780). From 1898 to 1914, the secondary school of the Baron Hirsch Foundation operated in Horodenka.
The large Horodenka synagogue was built on the site of an old wooden synagogue burned down by Russian troops in 1915 (then, after the fire, only the walls remained). In the 1920s, the Great Horodenka Synagogue was rebuilt. As a result of the reconstruction, the synagogue acquired an eclectic structure with classicist and modern elements.
After World War II, the desecrated synagogue was abandoned and the Jewish community did not recover. At first, a motorcade was located here, and today the former synagogue is used as a gym.