Painter Lucas Cranach the Elder (1472–1553) acquired this large property including the local pharmacy from the heirs of physician Martin Pollich von Mellerstadt. Moving in with his family in 1518, he moved his large workshop here and also ran the pharmacy. In around 1540, the rear east wing was built and is initially thought to have contained the workshop. A few years later, the workshop was moved to the newly built south wing. In 1550, when Lucas Cranach the Elder left Wittenberg, ownership of the property passed to his son, Lucas Cranach the Younger (1515–1586).
In the 16th century, young artists were trained here to work in the courts of European princes. Training was revived in 1996 when the Cranach Foundation established the School of Painting for youngsters. The workshop buildings were refurbished between 1997 and 2000 as an external project for Expo 2000. The front building, which now houses the Cranach Pharmacy again as well as a hotel, was completed in 2009.