Armenians settled in Lviv most willingly in the area of the Church of the Assumption of the Blessed Virgin Mary and St Gregory the Illuminator. The first, 13th-century church was wooden. Construction of the Armenian Cathedral began on the same site and under the same name in the second half of the 14th century. It was founded by the Kaffa-born Jacob, son of Shahinshach, and Panos, son of Abraham. The architect Dorchi (Doring), who was also employed on the St. George Cathedral, is mentioned as the author of the oldest part of the cathedral, which has survived to this day and was built between 1356 and 1363.

Temples such as the Armenian cathedral are rarely found in this part of Europe, as the architect referred to the churches of Armenia. Historians have found stylistic links with the famous cathedral in Ani and the church in Odjun, as well as with the 14th and 15th century temples of the Armenian colony in Kaffa in the Crimea. In Lviv, the building was constructed with a rather cramped interior, closed with three apses on the east side. What remains today is a chancel with apses and a dome on a 12-sided tambour supported by trompets. In the oldest part of the cathedral, late medieval painting decoration is fragmentarily preserved.

In 1363, King Casimir the Great established Lviv as the capital of the Armenian archbishopric and granted this national minority the right of judicial and confessional autonomy. The support of the authorities grew - especially after the Armenian Church in the Polish-Lithuanian Commonwealth accepted union with the Roman Catholic Church. In 1630, Bishop Nikolai Torosovich makes a profession of faith before Pope Urban VII and is entrusted with the dignity of archbishop. He also gains confirmation of no changes to the Armenian liturgy and rite. The nuns who resided in the Lvov Cathedral monastery adopt the Rule of St Benedict in 1660, adapting it for the Armenian liturgy.

The appearance of the Armenian cathedral changed over the years. Hoxha Andrew of Kaffa founded a new free-standing bell tower built in 1571 by Peter Krassowski. The previous belfry was destroyed by fire. In the 17th century, the nave was enlarged. Over time, new furnishings close to Roman Catholic churches, such as a pulpit and confessionals, appeared in the cathedral. This was due, among other things, to the fact that there had been a gradual latinisation of the Armenian church since the death of Archbishop Torosovich.

In 1784, as a result of the Josephine suppression, many of Lviv's churches and monasteries were liquidated or demolished. Two Armenian churches were also not spared - the 15th-century Church of the Holy Cross and the 16th-century Church of St Anne, together with the surrounding cemetery and the adjacent Antomak monastery (Armenian monks of the Rule of St Anthony the Hermit). The tombstones from the closed necropolis ended up in the courtyard of the Armenian Cathedral.

In the nineteenth century, proposals for the complete liquidation of the Armenian rite in the Polish lands became more and more strongly formulated. A fervent defender of the traditional rite became the preacher from Stanislawow, Fr Isaac Mikolay Issakovich, Archbishop of Lwow since 1882. His predecessor, Archbishop Grzegorz Józef Romaszkan, had already ordered the use of the Armenian Missal and liturgical books. In turn, thanks to Archbishop Issakovich, the Armenian Breviary was published, with the approval of the Holy See, and is still used today by the clergy of this rite.

When Fr Jozef Teodorowicz began his work as Archbishop of Lwow in 1902, he would pay particular attention to the cathedral, which was falling into disrepair and was too cramped for the faithful, with an interior that differed little from the Latin churches. Back in the 19th century, the free-standing bell tower was rebuilt, topped with several domes, and the first restoration work was undertaken at the turn of the century under the direction of Professor Jan Bołoz-Antoniewicz.

In 1908, expansion of the church began, continuing after a break caused by the outbreak of war. The architectural work, the design of which was based on the Old Christian tradition, was entrusted to Franciszek Mączyński. The original coffered ceiling over the 17th-century part of the nave is by him. The interior of the dome, built over the oldest part of the cathedral, is decorated with mosaics made in 1908 according to a design by Józef Mehoffer. Its motifs were taken from miniatures of the extremely valuable Skevrenskiy Gospel Book of 1197. In addition, the lower arches of the chancel vault were decorated with specially imported Venetian mosaics.

The chancel itself also received a new setting. In the 1920s, Witold Minkiewicz designed the great altar, the archbishop's throne and the semicircular balustrade. However, the three paintings by Jan Henryk Rosen - Homage to the Shepherds, Last Supper and Crucifixion - are particularly noteworthy. The same artist, using Armenian and Byzantine motifs in the spirit of modernism, also made some of the stained glass windows and stylised, monumental painting decorations of the walls of the rest of the cathedral. Among these, the Funeral of St Odilon was considered the most successful. Jan Henryk Rosen was offered a job in the Armenian Cathedral by Archbishop Teodorowicz himself, who was delighted with his paintings on themes relating to the Golden Legend of James de Voragine, exhibited by the painter at his first solo exhibition at the Zachęta in 1925.

The head of the Armenian Church had already decided to make new wall paintings in the Lviv Cathedral. The reason for this was the discovery of fragments of old polychromes that had emerged from under the plasterwork during the renovation carried out in 1908. The archbishop wished for a decoration that would cover the entire walls of the temple in accordance with Armenian tradition. Rosen had no experience when it came to wall painting. However, he was up to the challenge, which brought him great acclaim and recognition, although it has to be said that there was no shortage of criticism either. There is a curiosity associated with these works. Among the figures painted were numerous portraits of contemporaries. Although church law objected to such practices, Rosen suffered no consequences. The idea was very popular with the public and among those portrayed was Archbishop Teodorowicz himself as St Thomas Aquinas. The artist did not forget himself either. St John Nepomucen bears his features.

His magnificent frescoes on the walls of the Armenian cathedral brought Rosen new commissions, including the painting of the Defence of Czestochowa in the papal chapel at Castel Gandolfo, and he made polychromes and mosaics in numerous churches in the United States, where he moved in 1933.

Over the years, the area around the cathedral became one of the most beautiful corners of Lviv, known as the Armenian Alley, often compared to the streets of Jerusalem. The Cathedral's surroundings were fascinating: the cloisters of the southern courtyard, the eastern courtyard with the figure of St Christopher on a high column, and the northern courtyard with the remains of the cemetery, the nearby monastery of the Armenian Sisters, the palace of the archbishops, and the building that has housed the Armenian Archdiocesan Museum since 1932. Unfortunately, in 1945, the Soviet authorities ordered the closure of the cathedral, and some of the most valuable monuments were taken to Yerevan. Thus, no further expansion of the cathedral, which was planned by Archbishop Teodorovich, who died in 1938, was undertaken. For many years, the cathedral will serve as a museum storehouse for icons and other sacred art objects.

After the year 2000 and the visit to Lviv of the Holy Father John Paul II, the temple was restored to worship and taken over by the Orthodox Armenian Apostolic Church. In 2006. Ministry of Culture and National Heritage of the Republic of Poland for the first time succeeded in establishing cooperation with the current Hosts of the temple. The first completed project, coordinated by the Foundation for Polish Armenian Culture and Heritage, was the conservation of the stained glass window and skylight in the western dome of the cathedral. The stained-glass window, designed by Karol Zyndram Maszkowski, was presumably made in the Krakow stained-glass workshop of Władysław Ekielski and Antoni Tuch, as the latter was employed to decorate the painting of the dome, in the skylight of which the stained-glass window is located. It was subjected to conservation work and partially reconstructed by a team of conservators consisting of Ewelina and Robert Kędzielewski. The renovation of the skylight was carried out by a team of Polish specialists under the direction of Dr Janusz Mroz.