The first church of Simbirsk was built simultaneously with the fortress walls. In the year of its construction, Tsar Alexei Mikhailovich sent a silver altar cross to the city, adorned with gold, pearls, and precious stones, which housed the relics and parts of the vestments of 43 saints. Later, the church received other royal gifts. During the siege of Simbirsk by Stepan Razin, the church's clergy organized a procession around the city, taking place under fire. Ahead, they carried the cross with the relics, and one of the bullets left a deep mark on it. Soon, Razin retreated, and the cross, as a symbol of protection, was kept in the cathedral until its closure.

In 1694, a fire destroyed the wooden cathedral, and it was decided to build a new one out of stone. In 1702, the laying of two chapels began, and the construction was completed in 1712. The central part of the Nicholas Cathedral, almost square, had a large dome supported by four pillars and four small domes at the corners. Initially, the cathedral had a wooden bell tower, which was replaced in 1857 with a tall four-tiered bell tower. It initially stood separately but was later connected to the cathedral. Until 1844, the cathedral was called the Holy Trinity Cathedral, but after the construction of a new cathedral, it was renamed in honor of St. Nicholas the Wonderworker. The entrance to the cathedral was from the south side through a porch under the bell tower. The altar was separated by a carved iconostasis with ancient icons, which were adorned with precious coverings in the 1840s. The second, third, and fifth bishops of the Simbirsk diocese were buried in the cathedral. In 1898, the cathedral was rebuilt with funds from merchant N.Ya. Shatrov, making it more spacious. The cathedral was destroyed in the 1920s.