The limited edition T-shirt costs £20.45, with 15% of the retail price going to Amnesty International to support its human rights campaigns all over the world.
Through a partnership between Hard Rock and EDUN live, the T-shirt is available online or at Hard Rock's cafés, hotels or casinos.
The T-shirt is made from 100% African cotton and the back is emblazoned with the signatures of U2.
"I hope this T-shirt generates loads of cash for Amnesty International and their tireless work towards the release of prisoners of conscience all around the world," said U2's The Edge.
"Plus there's a guitar on it - so it's a win-win as far as I'm concerned."
Hard Rock has collaborated with the world's top bands over the last 20 years as part of the Signature Series. These include Jon Bon Jovi, The Who and John Lennon and Ringo Starr, raising millions for a variety of worthy causes.
Annie Balliro, Senior Director of Brand Philanthropy, Hard Rock International, said: "Hard Rock is honoured to have U2, legendary musicians and dedicated activists, join with us to raise funds and awareness for such an important organisation."
Watch U2 perform 'Vertigo' live below: