The American singer's manager Scooter Braun said the Manchester gig now has a "greater purpose" than ever after the country's second terror attack in two weeks.
Niall Horan, Justin Bieber, Katy Perry, Coldplay, Pharrell Williams, The Black Eyed Peas, Usher, Take That, Robbie Williams, Mumford & Sons and Little Mixtook to the stage and performed for free to raise at least £2m towards the We Love Manchester Emergency Fund.
Bono and his U2 bandmates sent an emotional video message to the huge audience at the One Love Manchester gig.
Currently in America on their Joshua Tree tour, which played Chicago June 4, he paid tribute to the victims of the terrorist attack and sent a message of support to those affected.
U2 at the United Center in Chicago, IL, June 25, 2015 (Photo by Wikimedia Commons)
"All our hearts are with you. All our hearts are with Manchester and with the UK and so many of our friends in this great city.
"We're broken-hearted for children who lost their parents and parents who lost their children from this senseless, senseless horror," he said.
"There is no end to grief, that's how we know, there's no end to love, a thought we're holding onto for these people. We'll see you again when the stars fall from the sky."
On June 3 seven people were killed and nearly 50 injured after three men drove a van into a crowd on London Bridge and set upon people in a crazed knife rampage.
Despite the atrocities, fans including those injured in the Manchester Arena on May 22, headed to the venue in their droves, proudly wearing clothes emblazoned with the slogan, "We stand together".
Mumford & Sons' Marcus Mumford was the first to take to the stage, asking for a minute's silence in tribute to those who have lost their lives in the two weeks prior, including the 22 killed in the bombing at the Ariana Grande concert at Manchester Arena.
In between renditions of Giants and Rule The World, Gary Barlow told the crowd: "Thank you everybody for coming out tonight, thank you for everybody watching at home, thanks to Ariana for inviting us tonight.
"Our thoughts are with everyone that's been affected by this.
"We want to stand strong, look at the sky and sing loud and proud."
Barlow then introduced his former band mate, Robbie Williams. Williams serenaded the crowd with his song Strong, changing the words to, "Manchester we're strong".
Concert-goers began queueing outside Lancashire Cricket Club's Old Trafford ground from 8.30am ahead of the One Love Manchester gig.
Ariana Grande at a 2015 Jakarta concert. (Photo by: Berisik Radio)
The event marked Ariana Grande's first return to the stage since suicide bomber Salman Abedi detonated a device.
All Grande fans who attended the gig on May 22 were offered free passes to the benefit concert.
Grande's manager Mr Braun said all the acts involved had shown "unwavering" support.
Questions were raised by fans about whether the One Love benefit gig would still go ahead in the wake of the latest terror attack in London.
However in a statement Mr Braun said: "After the events in London, and those in Manchester just two weeks ago, we feel a sense of responsibility to honor those lost, injured, and affected.
"We plan to honor them with courage, bravery, and defiance in the face of fear.
"Today's One Love Manchester benefit concert will not only continue but will do so with greater purpose.
"We must not be afraid and in tribute to all those affected here and around the world, we will bring our voices together and sing loudly.
"All artists involved have been unwavering in their support this morning and today we stand together. Thank you," he added.