The station sits on a Grade II listed viaduct, which was built in 1839 as part of the Manchester, South Junction and Altrincham Railway.

[3] To reduce load on this viaduct, the station unusually utilises laminated wood structures as opposed to masonry, concrete, iron or steel.

English Heritage describes it as a "building of outstanding architectural quality and technological interest; one of the most dramatic stations in England".

[7] As a key transition node for both north–south and east–west transpennine routes, it is a recognised bottleneck and is the most delayed major station in the United Kingdom according to a Which?

[8][9] In an attempt to obligate the DfT to provide funding for the Oxford Road upgrade to improve punctuality, Network Rail declared the Castlefield Corridor 'congested' in September 2019.

[12] The station was built on the site of 'Little Ireland', a slum "of a worse character than St Giles",[13] in which about four thousand people had lived in "measureless filth and stench"[14] (according to Friedrich Engels in The Condition of the Working Class in England) and of a gasworks which was relocated to the west.

A meeting of MSJAR contract ticket holders in 1863 included in its list of complaints the want of punctuality "especially as at Oxford Road station there is only one platform used for both passengers and milk".

[17] From 1854 onwards, Oxford Road served as the terminus for a service to Liverpool, independent of the London and North Western Railway(LNWR) (one of the joint owners of MSJAR).

Every train of the service was flagged down just short of the London Road platform and not allowed to proceed further, passengers being told they were liable to prosecution for trespass if they got out.

[24] To defeat the bill for the scheme, the LNWR then promised to cooperate with the MS&LR in widening the MSJAR and enlarging Oxford Road.

In October 1874, with Liverpool Central railway station now open, a letter to the press complained that with the additional services over the Cheshire Lines now using Oxford Road it was dangerously overcrowded.

Furthermore, it was rumoured that the LNWR was planning to run a competing service (via Broadheath and Warrington) between Oxford Road and Liverpool Lime Street: if this were true, then it would further worsen the congestion, and the Board of Trade should forbid it.

The whole station was again rebuilt and reopened on 12 September 1960, to a design by W. R. Headley and Max Clendinning of British Rail's London Midland region, encompassing three overlapping cones for the main structure.

Use of the station increased in 1988 when the Windsor Link between Deansgate and Salford Crescent opened, connecting lines to the north and south of Manchester.

[44] 'Pevsner'[45] calls it "One of the most interesting and innovative buildings of the period ... the most ambitious example in this country of timber conoid shell roofing" (p. 36) and "One of the most remarkable and unusual stations in the country both for the architectural form and the technological interest...it is the most dramatic and it is an important example of the deployment of timber to achieve large roof spans incorporating clerestory lighting."(p.