The Wannsee villa was built in 1915 by Ernst Marlier, a factory owner and Privy Commercial Councilor. Paul O.A. Baumgarten, a student of Alfred Messels, designed the building which contains 1,500 square meters (approximately 16,000 sq. ft.) of living space, and the large garden which measured 30,000 square meters (the size of a small park).

Baumgarten had already built several villas nearby, including one for the painter Max Liebermann. Marlier and his wife lived at Wannsee for only a few years before selling the house and premises to industrialist Friedrich Minoux in 1921.

Minoux himself was later arrested in an embezzlement scandal and sold the villa to the Nordhav SS Foundation set up by Reinhard von Heydrich in 1940. According to the museum, "The purpose of the foundation was to build and maintain vacation resorts for the SS Security Service (SD)." Heydrich wanted to use the Wannsee villa for "official functions and as a holiday resort."

The museum says that "Friedrich Minoux was not forced to sell. The Nordhav Foundation paid him 1.95 million Reichsmark, the market price." The sale included part of the furnishings and paintings. After Heydrich's death, the house was sold on February 4, 1943 to the Reich Security Main Office (RSHA) for the same price it had paid to Minoux. The stated purpose was the preservation of the building as a recreation center for men and officers of the Security Police. By 1945, the house had been inhabited first by Soviet Russian marines, and later by American officers.

After the war, the August Bebel Institute of the Social Democratic Party turned it into a residential adult education center, and from 1952 until 1988, the building served as a school hostel for the district of Neuköln. It was not until 1992, on the 50th anniversary of the Wannsee Conference, that the house was formally inaugurated as a memorial and Holocaust education site.