"Four people were killed and eight injured," Capt Ed Buclatin, director of public affairs at the Navy Installations Command at the Navy Yard, wrote on Twitter.
Local media reports said a police officer was among the injured.
The shots were reported to have been fired at the Naval Sea Systems Command headquarters at the yard in south-east Washington DC, the Navy said, adding that personnel at the yard were ordered to "shelter in place".
Dozens of emergency vehicles have converged on the site.
Nearly 3,000 people work at the command, which engineers, purchases, builds and maintains ships and submarines for the US Navy.
President Barack Obama has been briefed on the matter.
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