On 27 March 2020, the UK government announced that the building would be converted into an emergency hospital, intended to deal with the COVID-19 pandemic and with 1,000 beds.

The architect was Sir John Fowler and the engineers were Richard Johnson, Andrew Johnston and Charles Sacré for the three companies which formed the CLC.

It was constructed by Andrew Handyside and Co.[5] The substructure and masonry partition were provided by Robert Neill and Sons of Manchester.

Underneath the train shed is a large brick undercroft with intersecting tunnel vaults, above which were six platforms above street level which exited the station onto viaducts and bridges.

The Midland Railway (MR), one of the CLC's partners, used Manchester Central as its terminus for services including express trains to London St Pancras.

Beginning in 1938, the London, Midland and Scottish Railway (successor to the MR) ran two prestige expresses, The Peaks and the Palatine, stopping en route at Chinley, Millers Dale, Matlock, Derby and Leicester.

Between 1960 and 15 April 1966, during the electrification of the West Coast Main Line, Central Station was the terminus for the Midland Pullman, a streamlined blue six-coach diesel multiple unit.