Mampei Hotel's story began all the way back with the Kameya Inn back in 1764, during the height of the Edo Period, when Karuizawa was a major thoroughfare because of the era's post-station system. However, during the Meiji Restoration, the new Usui Pass was opened, and activity in Karuizawa declined. In the summer of 1886, two foreign visitors at Kameya Inn, the Canadian missionary Alexander Croft Shaw and an instructor at the Imperial University named James Main Dixon, were so enamored with Karuizawa's beauty that they promoted the town when they got back to Tokyo. By word of mouth, people once again paid attention to Karuizawa and Mampei's family was quick to capitalize on the influx, renaming the inn to Kameya Hotel in 1894, then finally to Mampei Hotel in 1896.
Due to its success, Mampei Hotel eventually moved to a new location in Sakuranosawa in 1902, where it was able to expand further. In 1919, Mampei Sato inherited the business and took charge of furthering its development. They would add the Alps Wing in 1936, with a design reminiscent of European mountain cottages. The hotel would be seized by the American Military in 1945, during their occupation of Japan after the Second World War, but this would also inspire the hotel to develop ways to operate even during winter. Eventually, control of the hotel would return to the family, and they would add the Asama and Atago Wings in the 1960s. Over the next decades, Mampei Hotel would host many esteemed guests, including the renowned musical artist John Lennon and his family, as well as the meeting between US Presidential Advisor Henry Kissinger and Japanese Prime Minister Tanaka Kakuei.
