The Franklin County Office of Emergency Management said the three casualties were airlifted from the Letterkenny Army Depot after the blast and that there was no threat to the public.
Their condition is not yet known but witnesses said a number of medical helicopters were called to the scene.
One witness said two employees at the base ran out of a building on fire, including “one with chemical burns”.
Another onlooker reported hundreds of staff members being evacuated from the facility after the blast.
Emergency responders treated some people at the scene and others have been taken to hospitals.
Depot staff members were asked to stay in their work areas until further notice.
They were told not post any information about the blast on social media or share information about it with the media or others.
Off-duty staff were told the stay away from the base.
A spokesman for the base said: “The incident is contained and will not affect depot operations or workforce safety elsewhere.
“There were injuries that fire and emergency services have treated and individuals have been transported to medical facilities.”
The 18,000-acre depot near the town of Chambersburg, about 160 miles west of Philadelphia, employs more than 3,600 people who help provide “responsive and sustainable readiness for the US and Allied Air and Missile Defence forces”.
Letterrkenny was established in 1942 and maintains and stores missiles and ammunition.