Barack Obama says the attackers will be held responsible for killing "patriots" on US soil as police hunt two gunmen still at large at the Washington naval yard.
Police say three men launched an attack on the US Naval Sea Systems Command Headquarters at the naval yard in Washington, killing a number of people and injuring others.
One of the gunmen has been shot dead but police are now hunting another two, who are said to be dressed in military uniforms.
The men launched their attack on one of the biggest naval command buildings in the US at around 8.20am - the early morning rush as people started work.
Navy officials said at least six people were killed in the attack, a number of others are being treated for gunshot injuries in local hospitals.
Washington DC Police Chief Cathy Lanier said that one officer had been hit in a shoot-out with the gunmen and one of the gunmen had been killed.
She said: "The big concern for us at the moment is that we potentially have two other shooters."
Police Chief Lanier said one of the men was white and dressed in a khaki, tan navy-style uniform with a beret, while the second man was black, aged around 50 and wearing olive drab uniform.
However, she said there was no indication that the men were actually military personnel.
She said that there had been multiple victims of the shootings but would not confirm an exact number.
Speaking ahead of a planned speech on the economy, President Barack Obama, who was being regularly briefed on the rapidly unfolding situation, said the attack was a "tragedy" and confirmed a number of people had been killed.
He said: "We are confronting yet another mass shooting and today it happened on a military institution in our nation's capital.
"It's a shooting that targeted our military and civilian personnel. These are men and women who were going to work doing their job protecting all of us.
"They are patriots and they know the dangers of serving abroad but today they faced the unimaginable violence that they wouldn't expect here at home."
He vowed to find those responsible and said that America would stand by the families of those who had lost their lives.
Witnesses had earlier described a gunman opening fire from the fourth floor, aiming down on people in the first-floor cafeteria. Others said a gunman fired at them in a third-floor hallway.
Patricia Ward, who works at the command centre, and witnessed the attack said: "It just happened so fast."
She said that a gunman had been shooting into the atrium and added: "but I didn't pay any attention to that, I just kept on running."
Responding to questions about the level of security at the base Ms Ward said: "It's not secure enough for me."
She said that staff had to have a card to get on to the complex and that without one it would be difficult to pass security.
Todd Brundidge, an executive assistant with Navy Sea Systems Command, said he and other co-workers encountered a gunman in a hallway of their building on the third floor.
"He just turned and started firing," he said.
Terrie Durham, an executive assistant, said she also saw the gunman firing toward her and Mr Brundridge.
"He aimed high and missed," she said. "He said nothing. As soon as I realised he was shooting, we just said, 'Get out of the building.'"
Officials at MedStar Washington Hospital Center said two shooting victims had been brought there.
Sky News US Correspondent Greg Milam said: "If it is confirmed there is more than one gunman it suggests a level of coordination, of planing, maybe something more than just domestic issues, maybe you start then to question whether there is a terrorist motivation."
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