Manchester Central Station was built between 1875 and 1880 by the Cheshire Lines Committee (CLC), and was officially opened on 1 July 1880. The engineers were Richard Johnson, Andrew Johnston and Charles Sacr© for the three companies which formed the CLC, the Great Northern, the Midland, and the Great Central.

While the main station was being built a temporary facility called Manchester Free Trade Hall Station (after a landmark building nearby) was in use from 9 September 1877. This consisted of two wooden platforms serving four tracks. When Central opened the temporary station was converted to become Manchester Central Goods.

The train shed is covered by a huge wrought-iron single-span arched roof, spanning 64 m.(210 ft.), 168 m.(550 ft.) long and 27 m.(90 ft.) high at the highest point. It was constructed by Andrew Handyside and Co.. The substructure and masonry partition were provided by Robert Neill and Sons of Manchester. The roof was originally covered with a mixture of slate and glass. Underneath the train shed there is a large brick undercroft with intersecting tunnel vaults. This was used for storage and was connected to the adjacent goods sidings by a carriage lift.

A wooden building was erected at the front of the station, housing ticket offices, waiting rooms and so on. This was planned to be a temporary structure, to be replaced by a grander edifice, for example a hotel and railway offices as at London St Pancras, but the provisional construction remained in use until the station closed. The Midland Hotel was built by the Midland Railway in 1898-1903 on an adjacent site.

The Midland Railway, one of the CLC's partners, at last had a secure Manchester terminus for its services, including its expresses to St Pancras. Beginning in 1938, it ran two prestige expresses, The Palatine and the Peaks, the former stopping 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. This stopped only at Cheadle Heath (now closed), before running fast to St Pancras.
Services through Millers Dale finished in 1968 when the line was closed. The station continued to provide local services for a while, but finally closed to passengers on 5 May 1969, when remaining services were switched to Manchester Piccadilly station.

Since closure it has been redeveloped as an exhibition and conference centre.