Other stars who took to the stage included Pharrell Williams, One Direction star Niall Horan, Justin Bieber, Little Mix and Imogen Heap also performed hits at the show while Katy Perry performed her hit Roar, saying: "We will not be silenced, Manchester".
In what may have been the most powerful moment of the show, Grande closed out the show by singing "Somewhere Over The Rainbow" alone onstage.
Before the show, Grande's manager Scooter Braun released a statement vowing that the show would go on.
After meeting the mother of victim Olivia Campbell-Hardy a few days prior, who told Ariana that Olivia would have wanted her to play her biggest songs at her show, Ariana scrapped the existing playlist to honour the late fan's wishes.
And Grande earlier sang My Everything with students from Parr's Wood High school in Manchester, comforting 12-year-old soloist Natasha Seth, who was overcome with emotion. "But love conquers fear and love conquers hate", she said.
The group had many in the crowd in tears.
"All we feel is love, resilience, positivity".
An armed policeman is seen with music fans at the One Love Manchester concert in Manchester June 4, 2017. "We ask the strong city of Manchester and the world to join us in making the statement that hatred and fear will never win".
She also thanked the scores of "strong and unified" people who refused to let terror attacks stop them from living their lives.
The mood at the concert was especially somber after a terrorist attack in London - which left seven dead and 48 injured after three men drove into a crowd and attacked with knives - occurred less than 24 hours ahead of the concert.
And Coldplay's Chris Martin brought Grande out so her could serenade her with his rendition of Oasis' Don't Look Back in Anger, which has become an anthem for Mancunians in the weeks since 22 people were killed as they exited Ariana's concert at the Arena.
"I don't want to feel or hear or see any fear in this building", U.S. singer Pharrell Williams told the crowd as he led them in a rendition of his hit single Happy. We love you so much. "But because of you we can now represent through this as a world wide community that we will be ready, we will be fearless we will be great and we will honor our children".