At its foundation in 1848, Queen's College occupied 45 Harley Street and within ten years acquired the lease on number 43 as well. The late 19th century saw extensive remodelling, and in 1898 a major bequest enabled significant changes to be made. These included the construction of the portico on the street front between numbers 43 and 45, which is still the most notable feature of the entrance to the College, and of the Main Corridor and Pfeiffer Hall. In 1921 the College was able to expand when the lease on 47 Harley Street was bought.

The second half of the 20th century witnessed major new developments. Kynaston House (49 Harley Street) was acquired in 1962, providing additional Library space and for a while accommodation for weekly boarders. Under two recent Principals, the Lady Goodhart (1991-99) and Miss Margaret Connell (1999-2009) modernisation has proceeded rapidly with new laboratories, ICT facilities, a Drama studio, a reworked kitchen and dining area and in 2007 a stunning refurbishment of the Pfeiffer Hall (re-named the Somerville Hall in 2010).  In 2011 work began in the basement of the buildings, and there has been significant opening up of the dining area and provision of better changing and bathroom facilities.