The monastery was founded in the first half of the 15th century by St. Makary of Yellow Water and Unzha. The name "Yellow Water" is associated with the Yellow Lake, on the shore of which St. Makary established the monastery. Over time, the Volga changed its course and engulfed the lake, resulting in the monastery being located on its bank. The central cathedral is consecrated in honor of the Holy Trinity, hence the monastery is called Trinity.

In 1439, Khan Ulu-Muhammed burned the monastery, killing the monks who had unlawfully occupied someone else's land, and took St. Makary captive. The Khan, upon learning of Makary's virtues, ordered his release. After his release, Makary asked to free the other captives, and 400 men and several women with children were set free. On their way home, they stopped on the right bank at the mouth of the Sviyaga River, where Makary decided to establish a new monastery. However, the Kazan Khan forbade them to stay, and they continued their journey to Galich land, stopping in the town of Unzha. The locals gladly welcomed Makary, but he withdrew to a deserted place 15 versts from the town, where he founded the new Yellow Water Makaryev-Unzha Monastery. Those wishing for a monastic life flocked to him. Soon the monastery was organized, but in 1444, at the age of 95, Makary passed away. Before his death, he bequeathed to establish a monastery on the bank at the mouth of the Sviyaga River, but his followers could not immediately fulfill this request.

Nikon studied Orthodoxy in the monastery for eight years, remaining a novice until 1624. The Old Believers believe that on his way to Unzha, he founded one of the Kerzhenets sketes, Olenyevsky, which split during the 17th century.

In 1620, a man from Murom named Avraamy renewed the monastery at the old site, gathering a monastic brotherhood. From this moment, the flourishing of the Yellow Water Monastery began. Avraamy died in 1640, after which the "Tale of the Renewal of the Yellow Water Monastery" was written. The monastery, located on the navigable Volga, became the center of a fair named after Makary, which was the largest in Russia and possibly in Europe. The income from trade contributed to the construction of stone buildings. After the church schism, the Kerzhenets River became a stronghold of the Old Believers. In 1817, for political reasons, the Makary Fair was moved to Nizhny Novgorod, leading to the decline of the monastery, which was soon abolished. In 1883, the monastery was restored as a women's monastery, and by 1917, about 300 sisters lived there. During the Soviet era, the monastery was closed, housing a children's home and an evacuation hospital, and in 1943 it became part of the Lyskov Veterinary Technical School.

Since 1991, the buildings of the monastery have been transferred to the Nizhny Novgorod Diocese, and in the same year, the Makaryev Yellow Water Women's Monastery was reopened, with about 25 nuns residing there. In 2005, Archbishop Georgy performed the rite of the Great Consecration of the Altar in honor of St. Catherine in the Assumption Cathedral. On August 7, 2007, the honorable head of St. Makary was transferred to the Makaryev Monastery from the Pechersky Ascension Monastery, and Archbishop Georgy consecrated the Trinity Cathedral.