The blaze at Naval Base San Diego in California was reported shortly before 9:00 am on Sunday (local time) on USS Bonhomme Richard, US Navy spokesman Mike Raney said.
Seventeen sailors and four civilians were taken to hospital with "non-life-threatening injuries", Raney said in a brief statement, AP reported.
Officials earlier said at least one person was treated for smoke inhalation.
The cause of the fire was under investigation and it was not immediately known where on the 255-meter amphibious assault vessel the blast and fire occurred.
The flames sent up a huge plume of dark smoke, visible around San Diego.
San Diego is the Bonhomme Richard's home port and it was undergoing routine maintenance at the time of the fire.
About 160 sailors and officers were on board, Raney said — far fewer than the thousand typically on the ship when on active duty.
The ship has the capacity to deploy and land helicopters, smaller boats and amphibious vehicles.
Two other docked ships, USS Fitzgerald and USS Russell were moved to berths away from the fire, Raney said.