Families who lost loved ones and those injured in the terror attack three months ago are expected to be among the 14,000 crowd at the sold-out gig, with funds raised going towards a permanent memorial for the victims.
Among the 22 people killed in the terror attack was Sheffield woman Kelly Brewster, 32, from Arbourthorne who suffered fatal injuries as she shielded her niece in the blast.
Some of those affected made a private pilgrimage this week, ahead of today's public reopening, to lay flowers at the spot where their loved ones died or were injured on May 22 .
Suicide bomber Salman Abedi detonated his device in the foyer of the venue at the end of an Ariana Grande concert, killing 22 and injuring scores of others.
The devastated area has been partly renovated and reopened for tonight's event titled We Are Manchester to show the city will not be defeated by terrorism.
Mayor of Greater Manchester Andy Burnham said: "The arena reopening will be a difficult and emotional night for everyone but it is an important event that will bring people together to remember all those affected by the horrific arena attack.
"This is the strongest possible statement that we can make to those that peddle hate. They will not change us, we will continue to stand together. They will never changeManchester."
A pre-show DJ set from Clint Boon will be followed by a performance from poet Tony Walsh, known as Longfella, with a recital of This Is The Place, a homage to the city ofManchester.
The event, headlined by Noel Gallagher's High Flying Birds, will include performances by The Courteeners, Blossoms and Rick Astley.
All profits raised will go to the Manchester Memorial Fund, a charitable trust overseen by the city's Lord Mayor to pay for the permanent memorial.
Terry O'Hara, project lead for the Survivors Assistance Network at the Tim Parry Johnathan Ball Foundation for Peace, on Thursday helped co-ordinate visits to the arena by around 400 people affected by the bombing.
Mr O'Hara said: "It was incredibly emotional and very dignified. It was a very emotional place. It got very busy, especially with many young girls."
He said a team of trained trauma specialists and mental health professionals will be on hand at tonight's event for anyone who needs help.
He added: "We are there ready to provide support. I'm hopeful it will be a poignant but happy occasion but if people need support we will be there for them.
"I think there will be a very positive atmosphere.
"There's also a thing about getting back to normal and life carrying on in defiance of terrorism, there's a symbolism to the arena reopening."
Additional security and screening upon arrival at the venue will be in place, with no backpacks or large bags allowed inside.
Chief Superintendent Wasim Chaudhry, of Greater Manchester Police, said: "I would like to welcome everyone heading into the city centre this weekend to attend the concert at the Manchester Arena.
"This will be the first event held at the arena since the terrorist atrocity which took place on 22 May and clearly the opening will hold significance for the people of Manchesterand all those affected by the attack.
"I would encourage everyone to arrive in a timely manner so that they can ensure they pass through the security checks and get into the venue without missing the start of the concert.
"Once again I would like to welcome everyone attending and I hope everybody has a fantastic time."
The event is being broadcast live on BBC Radio Manchester, X-fm and Key 103 radio stations.
Doors open at 5pm, with the main show starting at 7pm and the event expected to end around 11pm.