The line from Bletchley to Oxford was opened by the Buckinghamshire Railway (later owned by the L.& N.W.R.) in 1851. The Oxford station was built on the site of Rewley Abbey, a 13th century Cistercian monastery.

The contractors for the main building were Fox, Henderson who were completing The Crystal Palace at the same time, and they used similar - but not identical - prefabricated cast iron main structural components. The historic importance of this feature led to a Grade II* Listing. There were two platform faces partly under a glass-roofed train shed; the latter was replaced to a different design in 1888.

The Great Western Railway had opened its station in 1852 on an adjacent site, the location of the current Oxford railway station, and the two stations came under joint management in 1933. Rewley Road was closed to passengers by the London Midland Region of British Railways in 1951 and services transferred to the ex-G.W.R. station. The goods yard remained available for use until 1984 and was cleared in 1998. After the station closed to passengers the main building was put to commercial use.

Construction of a new building for Oxford University's Sa¯d Business School required the dismantling of the station building in 1999, with the financial support of the University. Parts of the goods yard were developed for housing. The station building components were moved to the Buckinghamshire Railway Centre at Quainton Road railway station, operated by the Quainton Railway Society Ltd.

The station lies in the far depths of "Metro-land", about 5 miles (8 km) west of Aylesbury in Buckinghamshire. The site is divided into two halves which are joined by two foot-bridges, one of which provides wheelchair access. Each side has a demonstration line with various workshop buildings as well as museum buildings. Separating the two halves is a Network Rail goods line, formerly the mainline used by the Great Central Railway and the Metropolitan Railway via the Metropolitan and Great Central Railways Joint Committee.

Oxford Rewley Road railway station now stands at the north-west corner of the site and serves as reception, visitor centre and display building. It is the sole surviving example of Sir Joseph Paxton's pioneering use of glass, iron and timber.