Rubio will travel July 8-12 and will take part in meetings in Kuala Lumpur with the 10-member Association of Southeast Asian Nations, whose foreign ministers are gathering there, the State Department said.
Rubio will seek to firm up US relationships with partners and allies in the region, who have been unnerved by Trump's global tariff offensive.
He might be in for an awkward reception.
On Monday, Trump hit Malaysia with a 25 per cent tariff and 40 per cent on Laos and Myanmar.
Trump also placed a 25 per cent tax on goods imported from Japan and South Korea.
The White House has warned that more countries will receive letters outlining new levies.
Indonesia has dispatched trade representatives to Washington and Thailand submitted a new trade proposal offering zero tariffs on many US goods.
Rubio's trip is supposed to be part of a renewed US focus on the Indo-Pacific and represents an effort by the Trump administration to look beyond the conflicts in the Middle East and Europe that have so far consumed much of its attention.
Last week, Rubio hosted Australian Foreign Minister Penny Wong and counterparts from India and Japan.
They announced a joint initiative to ensure the supply of critical minerals, a vital sector for high-tech applications dominated by Washington's main strategic rival, China.
Trump has announced that he reached a trade agreement with an important Southeast Asian partner and ASEAN member Vietnam and could reach one with India.
Rubio has yet to visit Japan or neighbouring South Korea, the other major US ally in north-east Asia, since taking office in January, even though Washington sees the Indo-Pacific as its main strategic priority given the perceived threat posed by China.
ASEAN countries have been nervous about Trump's tariff offensive and have questioned the willingness of his "America First" administration to fully engage diplomatically and economically with the region.
"There is a hunger to be reassured that the US actually views the Indo-Pacific as the primary theatre of US interests, key to US national security," said Greg Poling, director of the Southeast Asia Program at Washington's Centre for Strategic and International Studies.
