"We stand with the people of Orlando, who have endured a terrible attack on their city," the president said in a brief address to the nation.
While emphasizing that the motivations of the gunman are still under investigation, Obama said, "We know enough to say that this was an act of terror and an act of hate. As Americans, we are united in grief and in outrage."
As the FBI continues to lead the investigation of America's deadliest shooting, "We will go wherever the facts lead us," Obama said.
The president said that Sunday was "an especially heartbreaking day for all of our friends and fellow Americans who are lesbian, gay, transgender or bisexual."
The attack on the nightclub, Obama said, "is an attack on all of us."
While he did not explicitly call for more gun control measures, he said the shooting is "a reminder of how easy it is for someone to get their hands" on deadly assault weapons.
"We have to decide if that is the kind of country we want to be," he said, reiterating remarks he has made in reaction to previous mass shooting tragedies.
Obama urged Americans to say a prayer for the victims and their families.
"God give them the strength to bear the unbearable," he said. Americans, he added, "will not give into fear or turn against each other."
A heavily armed man opened fire in the crowded Pulse Orlando gay nightclub early Sunday, killing 50 people and wounding 53 in the deadliest shooting spree in U.S. history, law enforcement authorities said.
A federal law enforcement official told USA TODAY the suspect had been identified as Omar Seddique Mateen of Port St. Lucie, Fla. His father told NBC News that Mateen had recently expressed anti-gay sentiments. Members of Congress who were briefed by intelligence officials said the gunman reportedly pledged allegiance to the Islamic State.
Orlando Police Chief John Mina said the attack began at 2:02 a.m., when three police officers engaged the suspect in a gun battle outside the club. A hostage situation then took place inside, and a SWAT team was called in, Mina said. Police received updates from club-goers trapped inside, and decided to storm the club at about 5 a.m. The gunman was reported dead at the scene.