The monastery was founded by the venerable Nikita, a disciple and relative of Sergius of Radonezh, who had previously been the abbot of the Vysotsky Monastery in Serpukhov and the High-Pokrovsky Monastery in Borovsk. Initially, all the buildings of the monastery were wooden. In the 16th century, the wooden walls of the monastery protected Kostroma. In 1559, the construction of the Bogoyavlensky Cathedral began, the oldest stone structure in Kostroma. The initiator of the construction was Abbot Isaiah, and Prince Vladimir Andreyevich Staritsky, a cousin of Tsar Ivan the Terrible, became one of the major benefactors.

In the 16th century, two female monasteries were affiliated with the monastery: Anastasiev and the Exaltation of the Holy Cross. In 1569, Prince Vladimir Andreyevich Staritsky visited the monastery while leading an army to protect Astrakhan. He was ceremoniously welcomed by the monks led by the abbot, which caused discontent from Tsar Ivan the Terrible. At the end of the same year, Prince Vladimir was killed by the tsar's order, and in 1570, the tsar's wrath fell upon the monks, many of whom, including Abbot Isaiah, were executed.

The monastery suffered during the Time of Troubles. At the end of 1608, the troops of False Dmitry II, led by A. Lisovsky, besieged it. Despite the defense, on December 30, Polish troops broke into the monastery, looted it, and destroyed it. Eleven monks, five servants, and thirty-eight peasants perished.

In 1918, the monastery was closed, but the Bogoyavlensky Cathedral became a parish church until 1924. From 1925, the cathedral building housed an archive. In the 1920s and 1930s, the monastery walls and towers were destroyed, and the Nikolsky Church and chapel were ruined. In 1982, a fire occurred in the cathedral, destroying the remnants of 17th-century frescoes.

The monastery was revived as the Bogoyavlensko-Anastasiev Women's Monastery in 1990. In 1991, the Bogoyavlensky Cathedral became the cathedral of the Kostroma Diocese, and the Theodorov Icon of the Mother of God was transferred here. In 1991, services began in the Smolensk Church, and in 2006, the church in honor of Sergius of Radonezh and Nikita of Kostroma was restored. In 1993 and 1997, the western and hospital buildings were vacated, and in 2001, the eastern building. The monastery wall was restored, the cemetery revived, and a memorial cross was erected at the site of the destroyed Nikolsky Church. Two hotels were created for pilgrims and clergy.

In 2002, a monument to St. Great Martyr Theodore Stratilates was erected on the monastery grounds, consecrated by Patriarch Alexy II.

Currently, the Kostroma Diocesan Administration and Spiritual Seminary are located on the monastery grounds. Entry to the monastery territory is prohibited, with only the entrances to the Bogoyavlensky Cathedral and chapel open. An orphanage for girls and a nursing home for the elderly operate at the monastery.