In 1221, Saint Prince Georgy Vsevolodovich founded Nizhny Novgorod and built the first wooden church dedicated to Saint Archangel Michael. In 1227, he replaced the wooden church with a stone one, which became the court temple of the Nizhny Novgorod princes after the grand princely throne was established in the city. However, by 1359, the church had significantly deteriorated, and Grand Prince Andrey Konstantinovich built a new stone temple in its place, the walls of which have survived to this day.

Throughout its existence, the Archangel Cathedral has suffered from attacks and fires multiple times. By the early 17th century, it was in need of major repairs, which were carried out from 1624 to 1631 during the reign of Tsar Mikhail Fedorovich at the expense of the royal treasury. During the renovation, the appearance of the temple changed: the vaults were dismantled, and a stone tented roof appeared on the old walls, which has been preserved to this day. In 1672, an altar dedicated to Saint Evangelist John the Theologian was added to the cathedral, replacing the burned wooden church. Fires in the Kremlin in 1704, 1711, and especially in 1715 caused significant damage to the cathedral, and it was closed for services. In the 1730s, the cathedral was restored by the efforts of Vice-Governor Volynsky, who arranged a new iconostasis and provided the temple with necessary utensils. The cathedral was consecrated on March 18, 1732. In 1795, the altar of the cathedral was renovated by Prince Dolgoruky, who consecrated the altar not only in the name of the Evangelist John but also of Saint Prince Georgy, the founder of the city. During the independence of the Nizhny Novgorod Grand Duchy, the cathedral served as the court temple and later became the burial place of the descendants of Prince Konstantin Vasilyevich. Here lie Prince Vasily, son of Simeon Kirdyapa, his son Ivan Vasilyevich Gorbaty-Suzdalsky, Prince Ivan Vasilyevich, son of Vasily Kirdyapa, and Prince Vasily Yuryevich, nephew of Ivan Vasilyevich Kirdyapa. Also buried here are Princes Peter, Zinoviy, Zosima, Iona, and Princess Irina.

Among the ancient icons of the cathedral, the appearance of Archangel Michael to Joshua, dating back to the 14th century, the Kiev-Pechersk Icon of the Mother of God, icons of the Venerable Mary of Egypt, Saint Nicholas of Myra, and the Resurrection of Christ stand out. The cathedral houses a shroud embroidered with gold and silks, an altar cross with relics, presented by Boyar Golovin.

On February 16, 2006, President of Russia Vladimir Putin visited Nizhny Novgorod, laying flowers at the grave of Kuzma Minin in the cathedral's burial vault. In 2008, a monument to Prince Yuri Vsevolodovich and Bishop Simon of Suzdal was installed near the cathedral, which was unveiled on February 17. On that day, a festive liturgy was held in all the churches of the city, and the monument was consecrated by Archbishop Georgy. On March 16, 2009, nine bells were presented to the cathedral by deputies of the Nizhny Novgorod Legislative Assembly. On March 26, 2009, the largest bell, weighing 530 kg, was installed on the belfry. In September 2009, Patriarch Kirill visited the temple, honoring the memory of Kuzma Minin and performing a memorial liturgy, gifting the cathedral the Kazan Icon of the Mother of God.