The church was founded in the 16th century by the romanian ruler Mircea Ciobanul, under the name Church of the Annunciation. For centuries, the church served as a place of coronation of many rulers of Romania.
In 1847, the St. Anthony Church, which was located very close to the Annunciation Church, in the St. Anthony Square, was completely destroyed by the devastating fire of Bucharest, which broke out in an opposite building. In memory of the destroyed church, the Annunciation Church got its old patron, St. Anthony.
Shortly after the fire, the new St. Anthony Church was renewed by the austrian architect Johann Schlatter and received a neoclassical facade. The church got its original appearance back after it was restored by the romanian architect Horia Teodoru between 1928 and 1935.