According to the life of Macarius, after the destruction of the Zheltovodsk monastery by the Tatars, a new site was found on the high right bank of the Unzha River. Here, Macarius erected a cross, built a small hut, and dug a well, the water of which was considered healing. He moved to the bank of the Unzha with the permission of Khan Ulu-Makhmet. In 1444, Macarius passed away, and a wooden Makaryev church was built over his grave, followed later by the church of Flora and Lavra. The new monastic community was named 'Makaryeva Novaya Pustyn Zheltovodsky Monastery.' In 1596, Tsar Fyodor Ioannovich appointed a builder, monk David Khvostov, to the monastery, who in 1601 built a new stone church of Flora and Lavra on the site of the old wooden one, as well as a wooden bell tower. At that time, about 20 residents lived in the monastery, and in 1607, several rivers and lakes with lands were assigned to it. In the 17th century, the monastery experienced fires twice in 1650 and 1669. The third abbot, Igumen Zosima, replaced the old Makaryev church with a new ten-walled and five-domed one in 1625, with chapels in honor of the Annunciation of the Most Holy Theotokos and the saints Boris and Gleb. At that time, the monastery was surrounded by a new wooden wall, and a gate church was built in the name of Nicholas the Wonderworker and the Solovetsky miracle workers Zosima and Savvatiy. Archaeologist P. G. Inyagin claimed in 1994 that there was a settlement here from the 14th and 16th centuries. Ancient burials and wooden structures from the 17th century were found in the cultural layer of the monastery. A particular interest is represented by a collection of fragments of tiles associated with the beginning of active stone construction in the second half of the 17th century. The architectural ensemble was formed in the 17th and 19th centuries. Monumental construction began in the second half of the 17th century when the main structures were erected: the Trinity Cathedral, the warm Makaryev church, the Annunciation church with a refectory and bell tower, the Nikolsk church over the Holy Gates, and the building of cells. The Makaryev and Nikolsk churches were built by Soligalich stone masons Gavriil Antipyev and David Gavriilov Antonov. In 1732 and 1735, a stone Assumption church with hospital cells was built on the site of the old wooden cells, where Tsar Mikhail Fyodorovich stayed in 1619. In 1754 and 1764, a stone fence with four towers was erected. In the 19th century, many buildings of the monastery underwent repairs and reconstructions, but their original appearance was mostly preserved. An exception is the hospital cells, to which a two-story brick building was added in the first quarter and mid-19th century. In 1849 and 1854, a porch was added to the refectory of the Makaryev church.

In 1919, the monastery was abolished, and the brotherhood was expelled. In 1926, the first of the monastery's churches was closed, and in December 1929, the rest were closed as well. The relics of St. Macarius were transferred to the local history museum, and a machine-tractor station and grain warehouses were established in the monastery. In the 1930s, except for a small section and two towers, the fence was dismantled. In 1970, the Kostroma restoration workshop began work on the restoration of the monastery, which continued until the early 1990s under the guidance of architects L. S. Vasiliev and A. P. Chernov. Part of the lost walls was recreated, and church buildings were restored.

On July 16, 1993, by the decision of the Holy Synod of the Russian Orthodox Church, the Makaryev-Unzhensky monastery was revived as a women's monastery, and in January 1994, the entire ensemble of monastery buildings was transferred to the Kostroma diocese. In August 1994, Archbishop Alexander of Kostroma and Galich consecrated the first revived church, the Makaryev church. In 1995, the relics of St. Macarius were transferred to the monastery from the city church.

Restoration and repair works continue in the monastery. In 1999, the eastern section of the wall with gates was recreated. In 2001 and 2002, due to the deterioration of the foundations of the Annunciation church, urgent emergency work was carried out under the guidance of Evgeny Pashkin and Yu. A. Koval to strengthen the foundations and walls of the building, but the bell tower could not be saved. Under the guidance of architect S. V. Demidov, a project was developed to recreate the collapsed bell tower. The first monastic tonsure in a hundred years after the closure of the monastery took place in the monastery on April 5, 2019.