Beijing considers democratic Taiwan its own territory, ineligible for state-to-state relations, despite strong objections by Taipei, which has been complaining about rising Chinese pressure to force it into accepting Chinese sovereignty.
China regularly calls Taiwan the most sensitive and important issue between it and the United States, which does not have formal diplomatic ties with Taiwan but is the island's strongest ally and main weapons supplier.
Lai will travel to and from Taiwanese diplomatic ally Honduras via the U.S. cities of Los Angeles and San Francisco, in what is generally standard procedure for visits by Taiwanese leaders to Latin America.
The U.S. government will give "courteous reception of a high standard" to the Taiwan delegation and Lai will hold virtual meetings with unspecified U.S. politicians during his stops, the presidential office said.
"Since the inauguration, the Biden administration has repeatedly demonstrated its firm support for Taiwan with concrete actions," the office said. "We believe the two sides will continue to stably deepen Taiwan-U.S. relations on all fronts."
The U.S. State Department said Lai's transit will be "private and unofficial," and was in keeping with the United States' "one China" policy. Under this, Washington acknowledges Beijing's position that Taiwan is part of its territory though the United States does not endorse this stance.
James Moriarty, a senior U.S. official and chairman of the American Institute in Taiwan which carries out Washington's unofficial relations with Taiwan, will "greet" Lai in California, a State Department spokesperson said in an email.
China's Taiwan Affairs Office said Beijing firmly opposed any form of official exchanges between the United States and Taiwan. In a statement, it urged the United States not to send a wrong signal to Taiwan pro-independence forces.
Lai will attend the inauguration of new Honduran President Xiomara Castro, seeking to shore up ties as China ramps up diplomatic pressure against the island.
Taiwan's government has said it will work with Castro to deepen relations with the country, which is one of only 14 nations with formal diplomatic ties with Taiwan, although Castro has floated the idea of ditching Taipei for Beijing.
The United States has been eager for Honduras to retain relations with Taiwan as it worries about growing Chinese influence in its backyard.
China has been stepping up pressure to win over Taiwan's remaining diplomatic allies, last month re-establishing ties with Nicaragua, and has openly said it is aiming to bring down the number to zero.
(Reporting By Yimou Lee; Additional reporting by Michael Martina in Washington; Editing by Raju Gopalakrishnan, Angus MacSwan and Cynthia Osterman)