In 1629, Afanasy Vekov, a well-known compiler of clerical books, mentioned in the inventory of the city of Shuya that the wooden and poor Resurrection Church was a parish church. In 1655, the icon painter from Shuya, Gerasim Ikonnikov, created the Smolensk Icon of the Mother of God for it. In 1667, the church became a cathedral due to the miracles associated with this icon, which was named the Shuya-Smolensk Icon. Soon after, a five-domed stone Resurrection Cathedral was built on the site of the old wooden church. The inventory of 1709, compiled by voivode Yakov Sytyn, mentions the cathedral church of the Most Holy Sovereign and the Church of Nicholas the Wonderworker, both stone. Both temples were destroyed by a fire on May 12, 1770, but the cathedral was soon restored, although it was demolished 22 years later due to dilapidation.

The construction of a new church continued in 1792 and 1798 with funds from parishioners. On September 19, 1799, Bishop Viktor of Vladimir and Suzdal consecrated the cathedral, into which the surviving miraculous icon was transferred. After the consecration, the cathedral was adorned with paintings and a carved gilded iconostasis, which cost 12,000 rubles. The cathedral had five domes covered with gilded brass, with eight-pointed crosses made of the same metal. In 1810, the Italian architect Yakov Marichelli began the construction of the bell tower, which collapsed in 1819, reaching the fourth tier. The construction was completed in 1833 by peasant Mikhail Savateev under the guidance of provincial architect Yevgraf Petrov. The height of the bell tower was 49 fathoms and 2 arshins, and the spire, 10 fathoms and 1 arshin, was covered with white iron with gilded apple and cross.

In 1912 and 1913, the church was expanded, a new refectory was added, and a three-domed structure was built over the western entrance. At the end of the 19th century, the clergy included a protodeacon, two priests, a deacon, and three psalmists. Since 1889, a church-parish school operated at the cathedral.

In 1922, during the persecution of the Russian Orthodox Church, Lenin announced the confiscation of church valuables under the pretext of combating hunger. The district commission attempted to seize valuables from the Resurrection Cathedral, but on March 15, 1922, the faithful resisted, and gunfire was opened on them, resulting in four deaths and ten injuries. On May 10, 1922, after a trial, protodeacon Pavel Svetozarov, priest Ioann Rozhdestvensky, and layman Pyotr Yazikov were executed. These events are known in history as the Shuya case. On October 2, 1937, the cathedral was closed. In the summer of 1989, it was returned to the Russian Orthodox Church. For a time, the cathedral became a dependency of the Holy Nicholas Shartomsky Men's Monastery. Worship services resumed in the church, and the frescoes and iconostasis were restored. In 2012, the Shuya Diocese was established. As of January 1, 2018, the rector is Archimandrite David Semenikhin.