This house has been changed many times since it was built. In 1853 George Green bought a property with its existing house and garden. Green made additions or possibly completely rebuilt the house to create a Regency-style mansion. In the late 1850s it was sold to Luke Michael Cullen, who eventually sold it to Sir Samuel Way.

Sir Samuel Way is one of most well-known South Australians of the 19th century. You can still see many of his contributions to the city today. He was a baronet, a chief justice, a grand master of the Grand Lodge of the Freemasons in South Australia, and the chancellor of the University of Adelaide. He was also a noted philanthropist who gave generously to his community. 

In the late 1870s, Way refaced and extended the building. The new Italianate home included an impressive set of marble steps. As a man of standing in educational, political and social circles, Way often entertained distinguished guests there.

After his death in 1916, Montefiore again underwent major renovations. The second storey was removed to reduce its size.

Since 1948, it has been part of Aquinas College, a residential college of the University of Adelaide.