The Leadmill opened in 1980 inside a Victorian flour mill on Leadmill Road - a building that already had musical history. The upper floors had housed the Esquire, a 1960s club where a young Jimi Hendrix and the Small Faces had played. The new venue began life as a community centre, with a mission to promote arts education and provide leisure facilities for the young and the unemployed of Thatcher-era South Yorkshire. An alcohol licence was not granted until 1982, so for the first two years the building offered plays, training workshops, and live music only. A 1982 pantomime was directed by a young Jarvis Cocker, then a teenager still years from forming Pulp's classic line-up. That same September the venue hosted a Festival Against Unemployment with local bands New Model Soldier, Party Day and Agent Orange. Jazz For Lunch ran most Sundays. The Housemartins queued for their own 1984 gig and were turned away by the bouncers.

In 1988, Prince Charles came to look around. His remarks, recorded at the time, are worth preserving: "It houses a theatre, live music venue, educational and training centre, not to mention a restaurant, bar, nightclub, and, they say, it makes a profit!" His Royal Highness's amused tone about a charity that managed to balance its books captured what the Leadmill had quietly become - a serious cultural institution that nobody had quite decided to build, occupying an unfashionable corner of a post-industrial city. Through the 1990s the building became the Sheffield home of Gatecrasher's earliest nights, before launching its own house night RISE. Sheffield's Arctic Monkeys sold the venue out in 2005 faster than any other band had. A 2015 Music Heritage Award from PRS for Music was unveiled by Pulp on a BBC 6 Music broadcast from the stage.

When COVID arrived in March 2020 and Britain locked down, the Leadmill could not open. The staff did what the staff had always done: improvised. They bought 2,000 toilet rolls wholesale and sold them at cost when a corner shop nearby started charging £1 each - four for £1.83 was the venue's rate. The bar auctioned off memorabilia to pay wages. A Crowdfunder fed into the national #SaveOurVenues campaign. Billy Bragg streamed an online concert from his living room and raised over £15,000. The Leadmill did what music venues had always done in Sheffield: it kept going by any means available, and the city kept it alive.

On 31 March 2022 the Leadmill announced that its landlords, the Electric Group - operators of music venues in London, Bristol and Newcastle - had served an eviction notice. The Electric Group said they would continue running a music venue at the site. The Leadmill management said they owned the brand, and any successor could not use the Leadmill name. Bands rallied. Billy Bragg, Kaiser Chiefs, Reverend and the Makers and Manic Street Preachers all spoke out. Sheffield's five Labour MPs wrote jointly to the Culture Secretary. On 19 May 2023, Def Leppard played a one-off benefit gig at the venue where they had once rehearsed in their early days. The fight dragged on for three more years. On 27 June 2025, Miles Kane played the final headline set. The lights went down. 'My Way' played. The longest-running music venue in Sheffield had become a piece of British music history. What replaces it - whatever it calls itself - has a high bar to clear.