Following the underway, the ship known as Old Ironsides will reopen for free public tours.
The warship will also fire a 17-gun salute at Coast Guard Sector Boston, the former site of the shipyard where USS Constitution was built and launched in 1797.
It is the ship’s first underway in more than a year because of the coronavirus pandemic.
Public visits were suspended in March 2020 at the start of the pandemic, but the ship reopened in August only to close again in November.
The USS Constitution is the world’s oldest commissioned warship still afloat, and played a crucial role in the Barbary Wars and the War of 1812, actively defending sea lanes from 1797 until 1855.
It earned its nickname during the War of 1812 when British cannonballs bounced off its wooden hull.