The Cathedral of St. Nicholas the Wonderworker is older than the city itself, as it was built in 1766, while Myshkin was granted city status only in 1777. From that moment, the Nicholas Cathedral became the city’s church. It is remarkable that such a large stone building appeared in a small village that had not yet attained city status, and all within three years.

The history of the cathedral's construction is quite interesting. Alexander Petrovich Berezin, a first-guild merchant and the mayor of St. Petersburg, was born into a peasant family in the village of Yeremeytsevo, not far from Myshkin. His father was so poor that he had to pawn an icon of St. Nicholas the Wonderworker in a local tavern. More than twenty-five years later, having become wealthy, Alexander redeemed the icon and considered it a miracle that it had survived. In memory of this, Berezin built a church in Myshkin at his own expense. He was actively involved in charity and built three churches: besides the one in Myshkin, there were the Ascension Church in Kruglitsy (now Okhotino) and a church in St. Petersburg.

The Nicholas Cathedral was constructed between 1766 and 1769, although there are records that it served as a parish church with altars in honor of princes Boris and Gleb and Alexander Nevsky as early as 1764. The architect of the building is unknown, but there is a theory that the project may have been developed by P.Ya. Pankov.

The cathedral is designed in the classical style. The main space of the building is a perfect cube. A large refectory adjoins it from the west, next to which once stood an impressive bell tower. The building is adorned with a wide light drum with large rounded windows, richly decorated with stucco, and topped with a dome featuring a miniature onion-shaped cupola. The facades are decorated with Doric pilasters and archivolts, while the windows have modest symmetrical arches. The northern and southern sides of the facades are embellished with columns with triangular pediments.

In the 19th century, a chapel in the tent style was built in front of the church, funded by local merchants after the miraculous rescue of Emperor Alexander III from a train crash. However, the chapel did not survive to this day: it was destroyed during the Soviet era, and a monument to Lenin was erected in its place.

The interior decoration of the church was completed in 1777. Painter Trofim Kashintsev and the Korolyov carvers, serfs of the Kozhins, created a magnificent iconostasis. Many rare icons were lost during the persecutions against the church.

In the 1830s, after the construction of the new Assumption Cathedral, the Nicholas Cathedral underwent significant reconstruction: porticoes with columns appeared on the southern and northern walls, and the dome was altered. In the 1860s, the bell tower was completely rebuilt, which was later destroyed.

The fate of the Nicholas Cathedral during the Soviet era was tragic. In the 1930s, the building was handed over to local cultural authorities, and the bell tower was dismantled. In 1934, the cathedral was converted into a cultural institution, and on November 6 of that year, the anniversary of the October Revolution was celebrated here. Due to the rush, two fragments of the iconostasis carving were left above the stage. The last disco in this building took place on April 18, 2003.

On May 2, 2003, the cathedral was returned to the Russian Orthodox Church. In the summer of that year, it was discovered that the protruding part of the stage was made from icons of the iconostasis. Two side panels also survived, one of which had kept the icon of the Savior 'in the crown of thorns...' for 96 years. On March 27, 2004, a cornerstone laid on September 1, 1835, was found in the cathedral. Since 2004, services have resumed in the Nicholas Cathedral.

Extensive restoration work has been carried out in the cathedral. In 2010, Patriarch Kirill of Moscow visited the church during a trip to the Yaroslavl Diocese in honor of the 1000th anniversary of Yaroslavl. He wished God's help to all who participate in the restoration of the cathedral and gifted the church an icon of St. Jonah of Kiev. Today, the Nicholas Church in Myshkin is active, but its interiors still need restoration.