The band, who have sold more than 100 million records worldwide, will appear in the city as part of 11-date UK tour this December, when they will play their Hysteria album in full.
The five-piece, who performed at Sheffield Arena in December 2015, will also play their first ever show at London's O2 Arena during the tour, which is due to be announced today.
Def Leppard, who formed in Sheffield in 1977, have also finally landed on the streaming service Spotify today, where their entire back catalogue will be available for the first time.
Frontman Joe Elliot said: "It is with a mixture of relief and euphoria that we now see our entire catalogue finally getting a digital release.
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"Having embraced every other format with open arms, especially and more recently the re-emergence of vinyl, we're now going to be available to everyone everywhere, and, honestly, it's as exciting as the original releases were."