On the site of the Orthodox Cathedral Church of Sremski Karlovci there was an older church dedicated to St. Nicholas, which is mentioned in 1532-33. Today's cathedral is also dedicated to St. Nicholas. Construction of the Cathedral of Saint Nicholas in Sremski Karlovci began at the initiative of Metropolitan Pavle Nenadović ( 1749-68 ), who decided that the new church should be built in the Baroque, instead of the "traditional ", style. The plan for the new church was commissioned in Vienna, the builders and craftsmen were Kosta Cincarin and a German named Johannes. The plans for the caps on the towers on the west side of the building, as well as the domes, were designed by Zaharije Orfelin. The foundation of the new church was consecrated on the 7th of May 1758, and the works were completed in 1762.
This is a one-nave structure with massive walls of brick. The church is rectangular with a semicircular apse to the east and two high Baroque bell tower to the west. The interior is divided into five bays, of which the first, the west, is in line with the towers, the second and third form the narthex and nave, the fourth, the solea and the fifth, the sanctuary.
The entire interior of the church is decorative, polychromous. A renowned woodcarver from Novi Sad, Andrei Marković, was engaged to create the iconostasis, and the work lasted from 1776 to 1778. The iconostasis is a fully developed Baroque altar partition, very common in Vojvodina in the second half of the eighteenth century. In 1780, Teodor Kračun and Jakov Orfelin were contracted to paint the iconostasis. Their work represents the pinnacle of artistic achievement of Serbian baroque painting in Vojvodina.
In the first decade of the twentieth century, after a devastating fire Patriarch Lukijan Bogdanović initiated repair works. These lasted from 1907 to 1910, and gave the church its present appearance. Vladimir Nikolić, a recognized Serbian architect, was chosen as chief designer. In this restoration, the dome was removed, the roof construction was changed and significant adjustments to the facade were carried out. Alterations were made to the interior of the church. The current painted decoration of the walls and vaults, as well as images of God the Father on the altar, the apostles in the corners around the dome, and the frieze of angels in the elliptical dome date from this time. The walls are decorated with paintings on canvas by the famous Serbian painter, Paja Jovanović.
The Cathedral of St. Nicholas in Sremski Karlovci, with its baroque iconostasis, was declared a cultural monument in 1949, and categorized as a monument of great importance in 1990. The last major renovation of the church was completed in 2010 by the experts of The Provincial Institute for the Protection of Cultural Monuments. The church building was repaired, and the façade, the roof and the entire interior of the building with brick decoration, iconostasis, choirs, tables, stained glass windows, chandeliers, decorative floor tiles and other elements, restored. Archaeological research was performed in the yard and under the building. Underfloor gas heating and humidity regulators were also installed.