"We've endured too many of these tragedies in the past few years," Obama said, his voice cracking with emotion at times during a nationally televised appearance in the White House briefing room just hours after one of the worst shooting rampages in US history.
Obama deplored as a "heinous crime" the attack by a heavily armed gunman at a school in Newtown, Connecticut, that killed 28 people, including 20 children. The shooter is dead, police said.
"Our hearts are broken today, for the parents, and grandparents, sisters and brothers of these little children and for the families of the adults who were lost," Obama said.
"Our hearts are broken for the parents of the survivors as well, for as blessed as they are to have their children home tonight, they know that their children's innocence has been torn away from them too early and there are no words that will ease their pain," he said.
Obama said the United States had "been through this too many times," but while urging Americans to unite in grief, he stopped short of specifically calling for tougher gun-control laws.
"Whether it's an elementary school in Newtown, a shopping mall in Oregon or a temple in Wisconsin, or a movie theater in Aurora, or a street corner in Chicago, these neighborhoods are our neighborhoods and these children are our children," he said.
"And we're going to have to come together and take meaningful action to prevent more tragedies like this, regardless of the politics."
Talk of reining in America's gun culture is considered politically risky, and Obama avoided making such direct calls during his successful run for re-election this year.
Obama, who has two young daughters, looked grim when he entered the briefing room, and he paused and blinked hard after mentioning the ages of the dead children - from 5 to 10.
"I know there's not a parent in America who doesn't feel the same overwhelming grief that I do," he said.
Obama raised a finger and dabbed at the corner of his eye on several occasions. While speaking, he set his jaw several times. At the end of his statement, there was a tear visible below his left eye and that side of his face was slightly wet.
Obama has issued public statements before in the aftermath of shooting massacres.
Following the killing of six people at a Sikh temple in Wisconsin in early August, Obama said such incidents should prompt soul-searching by all Americans.
But when asked whether he would push for further gun-control measures in the wake of the shootings, Obama said at the time only that he wanted to bring together leaders at all levels of American society to examine ways to curb gun violence.