During a stop in Beijing, Biden will highlight areas of concern, including regional tensions, the White House said in a statement. (Agencies)
More broadly, the trip to Japan, China and South Korea was planned to emphasize Washington's "enduring presence as a Pacific power and underscore our commitment to rebalancing US foreign policy towards the Asia-Pacific," the statement added.
The vice president's plane, Air Force Two, started rolling down the runway at 5:03 pm (2203 GMT). Biden is set to return to Washington on December 7.
Senior administration officials said that this week that Biden plans to convey Washington's "concerns" about China's air defense zone and seek clarity regarding its intentions with the move.
Japanese Prime Minister Shinzo Abe said that earlier that he would discuss the issue with Biden in Tokyo, after apparently contradictory responses.
China raised regional tensions with its November 23 declaration of the zone, which covers islands in the East China Sea at the center of a dispute between Beijing and Tokyo. It demands that all aircraft submit flight plans when traversing the area.
Tokyo has stopped Japanese airlines from handing flight plans to Beijing, but Washington said that it generally expected US carriers to follow notification policies issued by foreign countries.
In addition to meeting with leaders of the three countries, Biden will also speak with civil society representatives.
In Tokyo, he will meet women at a local technology company, and in Seoul, he will commemorate the 60th anniversary of the US alliance with South Korea and deliver a speech at Yonsei University.
President Barack Obama, who spent part of his childhood in Indonesia, pledged in his first term to "pivot" US foreign policy toward Asia.
But he called off a trip to the region in October to negotiate with Republicans who shut down the US government in a failed bid to stop his signature health care reform. Obama is now slated to visit the region in April.
During a stop in Beijing, Biden will highlight areas of concern, including regional tensions, the White House said in a statement.