In 1919, Karl (Carl) Emanuel Herzig opened Galerie St. Lukas Herzig & Loibl Ges. m.b.H. at Palais Pallavicini, located at Josefsplatz 5 in Vienna’s 1st district, , where he acted as managing director. The business purpose was trading in art and jewellery, antiques and carpets, publishing printed works and holding auctions. After the partner Anton Johann Loibl left the company in 1920, the name was changed to Galerie St. Lucas Herzig & Loibl, Ges. m. b. H. in Liquidation. In 1922, Loibl and Rudolf Richter founded the general partnership Loibl & Co. located at Himmelpfortgasse 3 in Vienna’s 1st district, a commission business for oil paintings and antiques. The first documented auction of paintings, sculptures and decorative arts took place at Galerie St. Lucas in 1921; the paintings to be sold were appraised by the art historian Gustav Glück. Until its deletion from the commercial register in 1923, the gallery also organised exhibitions, for example with works by Erika Abels d'Albert. In 1924, Herzig founded the sole proprietorship Galerie St. Lukas at the old location. After the entry of two partners, the academic painter Ludwig Fürst (1887-1950) and Adolf Fritz Mondschein, born on 26 March 1894, son of Julius Siegfried Mondschein and Adele, née Blümel, the antiques shop was continued from 1925 as a general partnership with a focus on the art trade under the name Galerie Sanct Lucas Carl Herzig & Co. Fürst left the company in 1927. One year after the death of company founder Karl Herzig in May 1930, his widow Julie (Jula) became a partner.

Shortly after the annexation of Austria to the National Socialist German Reich, the art historian Robert Herzig, the son of Julie Herzig from her first marriage to the secondary school professor Robert Sedlacek, joined the company in April 1938. He had been adopted by the childless Karl Herzig in 1919 and had completed his studies in 1935 with a dissertation on Gothic mural painting in Carinthia from 1380 to 1450. At the end of May, a few days after the foundation of the Vermögensverkehrsstelle (VVSt) (Property Transaction Office), Julie and Robert Herzig concluded a “dissolution agreement” with Mondschein, who was persecuted as a Jew: He was to leave the company with retroactive effect from the end of April, leaving Robert Herzig with sole power of representation. Mondschein, who had a 50 percent share in the gallery and a 60 percent share in the net profit, had to agree to take over an outstanding debt owed to the company by his cousin Eugen J. Schwabach in New York (approx. RM 93,000) in full. The VVSt approved the application submitted in June for the sale of Mondschein's company share to Robert and Julie Herzog in August 1938. In his Declaration of Assets completed in mid-July 1938, i.e. after the purchase agreement had been signed, Mondschein had valued his company share at only RM 17,850, a fraction of the estimated value. The inventory of his apartment at Cottagegasse 48 in Vienna’s 18th district, had been valued at approximately RM 10,000 by Franz Hartmann, appraiser of the execution court. Mondschein fled with his first wife Berta (Betty), née Wassermann (1896-1992), immediately after the November pogrom, first to England and from there to the USA in 1939. During the Nazi era, Galerie Sanct Lucas submitted numerous export applications to the Central Office for the Protection of Monuments in Vienna, with the Munich art dealer Julius Böhler, Hans W. Lange in Berlin, Pieter de Boer and Paul Cassirer in Amsterdam and Hans Bammann in Düsseldorf listed as recipients. However, these business relationships only partially reflect the gallery's intensive involvement in the art trade during the Nazi era. In 1939, for example, Robert Herzig sold the painting The Beggar Children by Ferdinand Georg Waldmüller, which had been seized on behalf of the Central Office for the Protection of Monuments and was intended as a gift for Adolf Hitler, to the Reich Foreign Minister Joachim von Ribbentrop and arranged for it to be exported to Germany. The gallery also worked with Hans Posse, Hitler's special representative for the planned museum in Linz, and acquired objects from expropriated collections via the Dorotheum in Vienna.

In 1946, Robert Herzig registered Mondschein's business share as expropriated assets, but explained that Mondschein, as a “fatherly friend”, had himself suggested the transfer “to enable him to leave the country and set up a business abroad” and had received “full pro rata compensation in money and goods” with a total value of approximately RM 135,000. There were no restitution proceedings. In 1947, Mondschein confirmed in an affidavit that he no longer had any claims against Galerie Sanct Lucas. In 1960, the latter repeated to the Vienna Financial Directorate that it was in business contact with its former partner and had “long since settled the dissolution values by mutual agreement”. Mondschein, who had changed his name to Frederick Mont in the USA, was back in his traditional line of business in New York City and played an important role in the transatlantic art trade. Among other things, Robert Herzig brokered a portrait by El Greco from the collection of the Jewish industrialist Julius Priester, who had fled to Mexico in 1939, to Mont, who also made numerous sales to US museums and maintained particularly close business relations with the art dealer Victor D. Spark (1898-1991) and the Newhouse Galleries. Frederick Mont died in 1994 at the age of one hundred; his grave is in Totengut cemetery in Chur (Switzerland). After Robert Herzig's death in 1987, the Sanct Lucas Gallery remained in the family and is still managed by Roman Herzig at its old location.

In 2012, the Art Restitution Advisory Board recommended the restitution of the oil painting In the Monastery Library by Eduard Grützner from the collection of August and Serena Lederer and their daughter Elisabeth Bachofen-Echt to the heirs. The painting, which had been stored at the Kirchner shipping company in 1938, was acquired in 1942 after having been seized by the authorities via the Galerie Sanct Lucas from the Linz special commission. It was transferred to the Central Collecting Point in Munich in 1945 and to the Österreichische Galerie in 1987. Two paintings by Gustav Klimt, Bauernhaus mit Birken and Dame mit Federboa from the Hermine Lasus Collection, were also restituted by the Austrian Gallery on the basis of an advisory board decision in 2000. They had been purchased by the Galerie Sanct Lucas in 1939 and acquired by the museum in 1950 and 1961 respectively.