The Newtown shooting is the second deadliest school shooting in U.S. history. It is surpassed only by the 2007 Virginia Tech shooting with 33 shot and killed, including the shooter.
The memorial service had been delayed nearly an hour as Obama met privately with first responders and families of the victims in classrooms of the high school.
The president walked in shortly before 8 p.m., gave a brief wave to the room full of parents, friends and neighbors, before taking a seat in the first row. He was met with a standing ovation.
"We needed this. We needed to be together, here in this room, in the gymnasium, outside the doors of this school, in living rooms around the world, we needed to be together to show that we are together and united," said Rev. Matt Crebbin, senior minister of the Newtown Congregational Church, who opened the ceremony.
"We gather in such a moment of heartbreak for all of us in Newtown," he said. "We gather especially mindful of family and friends and neighbors among us who have lost loved ones by an act of unfathomable violence and destruction.
"These darkest days of our community shall not be the final word heard from us."
The audience showed no signs of impatience, despite the delayed start. They sat quietly until a group of state police arrived at the already packed high school auditorium, but then stood to give the police a standing ovation and hugs.
Pat Calabrese and Rob Frate, two fathers whose third graders are students and best friends at the school, told reporters before the memorial that they knew several of the victims, but found comfort in tonight's services.
"It's bringing us all together for one thing, so we can see each other and talk without obstacles in front of us, to see the government and the United States cares as much to be here," Frate said, although he added the next few days would be the toughest.
"We all support each other and I think that's the beauty of Newtown," said Calabrese. "Everyone here in this room and outside this room can walk anywhere inside the school, outside the school, hug each other, shake hands, and just comfort each other. And we all know that."
The president's reaction to this tragedy in New England has been his most publicly emotional. On Friday, tears collected in his eyes as he addressed the nation.
But the president has also been more directly political in the immediate aftermath of these killings, as national discussions simmer over how to move forward and what, if any, policy is needed to prevent future violence. The president said on Friday it was time for "meaningful action" to prevent such tragedies, "regardless of the politics."
It is a subtle but noticeable shift for Obama, who has not actively pursued stricter gun control during his four years in office despite pledges to do so during his 2008 candidacy.
Although the White House says it needs support from Congress to move forward with strong legislation, it is also known that many politicians shied away to such reforms during the 2012 campaign season out of fear of alienating potential voters.
But with so many victims, and so many of them so young, a bipartisan group of lawmakers and activists sprung up over the weekend suggesting now was the time to push gun control.