Grande helped Victoria Monet perform her song, "Better Days", and the Black Eyed Peas sang their hit, "Where Is The Love?"
Will I Am took the opportunity to praise the efforts of emergency services and the courageous people of London and Manchester.
The concert raised money for victims and those injured in the suicide bombing that struck at Grande's May 22 show. The people are some of the most special I have ever met in my life.
Cyrus picked up his set with an emotional performance of her new song Inspired.
"Manchester, we're gonna be all right", she yelled.
Scooter Braun, Grande's manager, introduced the singer by first thanking Manchester, the United Kingdom city's first responders, and the "world class artists who journeyed here on such short notice" to perform at the One Love Manchester benefit concert.
Other artists were much more outspoken during their sets, especially Justin Bieber.
Tonight the U.S. star Ariana Grande will be back in the city for the One Love Manchester concert. But because of you, as a worldwide community, we will be fearless, will will be great and we will honor our children.
Some fans questioned whether Sunday's show would go on after three men drove a van into a crowd on a London bridge Saturday night before leaping out and stabbing numerous people in nearby bars and restaurants. The attack killed 22 and wounded dozens.
The show is being broadcast live across the globe.
The singer, who at times got emotional during her performances, blew kisses at her fans who attended last month's ill-fated concert.
The benefit concert will begin at 2 pm ET.
All of the incredible singers and bands gave the event their all throughout the evening, but it's hard to top seeing them all together, singing with one voice, one last time before the concert came to an end.
They say the auto and knife rampage in London on Saturday did little to ease their worries.
Tipping says: "We can't let them stop us".
The Manchester concert came the day after attackers targeted the heart of London, killing seven people.
Take That, who are from Manchester, followed Mumford with fun energy that the crowd danced to.