In 1813, the innkeeper Jonas Freinsheim built the two-storey hotel "Zum Deutschen Haus" in front of the Sonnenberger Tor, which was acquired by the innkeeper Johann Friedrich Goetz in 1819 and renamed "Gasthaus zum Nassauer Hof".

Around 1850, the house was extended and thermal baths were built, which were fed by the Spiegel spring. A representative hall, the so-called Marble Hall, was built around 1865 according to plans by Philipp Hoffmann. Finally, the owners commissioned the architect Alfred Schellenberg to build a luxury hotel on the site of the old inn, which had been demolished, and the theater, which was demolished in 1896. The Marble Hall was integrated into the new building erected between 1898 and 1907. The building complex, which framed Kaiser-Friedrich-Platz on the north and west sides, was built in neo-baroque style and featured two opulent domes above the corner risalits. In 1903, the building was the venue for a meeting between Kaiser Wilhelm II and Tsar Nicholas II.

The Hotel Nassauer Hof had around 200 rooms, which were equipped with electric light and running water. The bathing and spa facilities, which offered every kind of medical treatment including X-ray treatment, were famous. The Hotel Nassauer Hof had its own hot spring and shared in the mineral springs of the "Spiegel" and "Pariser Hof" hotels. At the beginning of the 20th century, it became the property of a public limited company.

After the First World War, it was confiscated by the French; in the summer of 1921, the German Minister of Reconstruction Walther Rathenau and his French colleague Louis Loucheur met here. In 1923, the industrialist and politician Hugo Stinnes (1870-1924) acquired the Hotel Nassauer Hof, after whose death it became the property of Stinnes AG. In 1940-44, it was the seat of the German Armistice Commission. Towards the end of the war, it was used as a military hospital, as it had been at the end of the First World War.

At the beginning of February 1945, the Hotel Nassauer Hof burned down after an air raid; the roof area was destroyed, while the neo-baroque facades were largely preserved.

Today, the Hotel Nassauer Hof is owned by Hotel Nassauer Hof GmbH and has 135 rooms, 23 suites, a presidential suite and a luxurious wellness area with a thermal swimming pool.