Although the town of Manchester existed from medieval times (and had previously been the site of a Roman settlement), the area now designated as the Northern Quarter was not fully developed until the late 18th century.

The area now between Shudehill and Victoria Station was first built upon in the 14th century, as the village of Manchester expanded as a local centre for the wool trade.

In the early 18th century, Oldham Street was apparently "an ill-kept muddy lane, held in place on one of its sides by wild hedgerows".

Heywood also produced a newspaper, on which he refused to pay duty — a radical gesture, since in those early days of the British Labour Movement, taxes were used to stifle free expression.

Haslam notes that a debate in the 1830s between one Dr Grinrod, a temperance activist, and Mr Youil, a brewer, attracted around three thousand spectators.

[12] The development of Smithfield Market and the continued growth of the cotton industry helped to foster economic activity in the Northern Quarter into the 20th century.

A street dancing culture emerged in the early part of the 20th century, with "dozens of young people performing polkas, waltzes and schottisches to music provided by Italian organ-grinders".

Following the Second World War, attention focused away from the Northern Quarter as Manchester began to build itself a modern city centre in the ruins left by German bombers.

[15] Although no official figures are kept (the Northern Quarter is not recognised for administrative purposes), it might be estimated that a little over 500 people now live in the area, which is split between the city centre and Ancoats and Clayton wards.

Over time, certain types of business were attracted to the area, which offered low rents and an alternative feel to the typical British high street.

This became the main strength of the Northern Quarter — today it is known for hip, independent stores, cafes and bars, and for offering a distinct alternative to the shopping experiences to be found elsewhere in Manchester city centre.

For Dave Haslam, the Northern Quarter became the last refuge of the Manchester music scene in the 1990s: "A community, of sorts, had developed around music-makers wedded to experimentalism, from Andy Votel to Waiwan, nurtured at club nights such as Graham Massey's Toolshed and Mark Rae's Counter Culture ...

The Northern Quarter also hosted the Big Horn sculpture, which was removed in 2017 to make way for the new SyNQ residential development, but is hoped to be erected again on nearby Afflecks Palace once work is completed.

[19] While the area around Dale Street has been used as 1940s New York for the 2011 Hollywood superhero film Captain America: The First Avenger,[20] the 2019 Sky TV production of Das Boot.

A 2003 planning document[23] stated: The Northern Quarter (N4) is strategically placed between the main Manchester retail and commercial core, Piccadilly Gateway, Ancoats and Shudehill.