The long, gabled house that stood in the Florhof's current location can first be seen in Murer's city view of 1576, and appears much the same in Merian's of 1642. A plan that matches this house's 16th and 17th century appearance can be found in the city's building archives. The house's first listed owner is one Hans Heinrich Hoffman, who was elected speaker of the Zurich City Council in 1634. In 1642 sold the property to the city for 3600 florins; the city needed the property for a land exchange with Squire Hans Ulrich Grebel-Holzalb (who had been the bailiff of Castle Laufen am Rheinfall). Later, in the census of 1682, Hans Konrad Heidegger is listed as the resident, and the property itself was transferred or sold to Captain Hans Jakob Oeri (1690–1758). In 1715 Oeri married Dorothea Gwalter, the daughter of the landlady of the "Krone vor dem Kronentor" and it was he who built a small manufacturing plant on the site of Florhofgasse 2. There he produced wool muslin and made himself Zurich's first florin-millionaire. Oeri had two children: one, Anna, married the guild master craftsman Hans Kasper Werdmüller, tore down her mother's house, and built what is today the Rechberg. The other, Felix, married Elisabeth Lavater and lived a privileged life as the rich heir in “Unteren Schönenberg”, which remained in the Oeri family until 1811. The next owners were the councilman Hans Konrad Finsler, founder of the bank that goes by his name, and, from 1830 on, the silk trader Squire Gottfried von Meiss-von Reinhard (1784–1858). His firm, “Meiss-Reinhard, Seiden und Floretseide” ("Meiss-Reinhard, Silk and Flowered Silk") probably gave the property its current name.

After several further changes in ownership the beautiful old noble house became, in 1907, a pension, and was bought by Hans Beckel in 1925. He renovated the entire property in 1974. Between 1960 and 1993 Lilo and Hans Schilter ran the hotel.

The hotel was completely renovated and refurbished again between 1994 and 1997. 1999 saw the addition of a small banquet room in the vaulted cellar, and two junior suites beneath the eaves. In 2006 the facade was lovingly restored. And in 2007 the Florhof celebrated 100 years of hospitality.