The Izumo is escorting a US supply vessel within Japanese waters.
The US ship is heading to refuel the naval fleet in the region, including the Carl Vinson aircraft carrier group.
North Korea has threatened to sink the Carl Vinson and a US submarine, amid rising tensions in the region.
On April 30, North Korea also carried out a failed missile test, despite repeated warnings from the US and others to stop its nuclear and missile activity.
According to The Japan Times, the 249m-long Izumo can carry up to nine helicopters, and resembles US amphibious assault carriers.
Kyodo news agency said it was leaving its base in Yokosuka south of Tokyo to join the US supply ship, and accompany it to waters off Shikoku in western Japan.
Under PM Shinzo Abe, Japan is gradually pushing the limits of what its modern and powerful military is allowed to do, and with tensions high on the Korean peninsula.
Japan’s post-World War Two constitution bars its military from using force to resolve conflicts except in cases of self-defense.
The Izumo is the first warship deployed outside of military exercises under new laws passed in 2015 that allow Japan to come to the aid of an ally under attack known as “collective self-defense”.
Shinzo Abe’s government, which pushed for the change, faced criticism that the new laws could lead Japan into unnecessary wars abroad – something the prime minister has rejected.
The Izumo’s deployment follows recent joint exercises conducted by Japan and the US, and other naval developments.
A French amphibious assault ship arrived in south-west Japan on April 29 for an exercise also involving Japanese, US and British naval forces. South Korea has been conducting joint exercises with the US as well.
China last week also launched its second aircraft carrier.
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