Biden and Vietnam's ruling Communist Party chief -- the country's paramount leader -- struck a "comprehensive strategic partnership" as Washington pushes to boost its network of allies around Asia and the Pacific.
The United States sees manufacturing dynamo Vietnam as an important part of its plan to decrease reliance on China for supplies of strategic resources, and the new pact includes agreements on semiconductors and rare earths.
Executives from tech behemoth Google, chip makers Intel and GlobalFoundries, and aviation giant Boeing joined Biden and Secretary of State Antony Blinken for an "innovation and investment summit".
They held talks with senior figures from a host of leading Vietnamese tech and manufacturing companies including electric car maker VinFast, internet firm VNG and digital wallet Momo.
At the talks, Biden announced that flag-carrier Vietnam Airlines had agreed a $7.8-billion deal with Boeing to buy 50 medium-haul 737 airliners.
Other deals announced include Microsoft developing a "generative AI-based solution tailored for Vietnam" and NVIDIA teaming up with local companies to deploy artificial intelligence in the cloud, automotive and healthcare sectors.
- Semiconductor security -
The new partnership includes an agreement on semiconductors, with the United States committing to help Vietnam develop its capabilities and expand production, including by funding workforce training.
Tiny semiconductors are vital to modern life, found in every electronic device from children's toys and smartphones to electric cars and sophisticated weapon systems.
Biden moved last month to restrict US investment in Chinese technology in sensitive areas including semiconductors, quantum computing and AI.
With Washington looking to diversify and strengthen its supply chains after a series of shocks hit the global economy, it is increasingly looking to Vietnam, which has the world's second-largest deposits of rare earths -- another strategically vital resource -- after China.
The White House highlighted US investment in chipmaking in Vietnam, pointing to a new $1.6 billion factory near Hanoi due to start operations soon.
- China difficulties -
Biden insisted Sunday that he did not want to "contain" China, but accused Beijing of seeking to change the rules of the international order.
And in their joint statement, Biden and Trong launched a fresh broadside at Beijing in the sprawling, multi-state territorial row over the South China Sea.
They warned against "threat or the use of force", days after the latest clash involving Chinese vessels, and insisted the competing claims to the strategic waterway must be settled under international norms.
Beijing claims almost the entire sea, through which trillions of dollars in trade passes annually, and has ignored an international court ruling that its assertion has no legal basis.
The president met Chinese Premier Li Qiang -- the country's number two leader -- on the sidelines of the G20 summit in Delhi on Sunday.
Biden said the major economic problems Beijing was wrestling with would limit its scope for action, particularly on Taiwan -- which China regards as a renegade province.
"China has a difficult economic problem right now for a whole range of reasons that relate to the international growth and lack thereof and the policies that China has followed," he said, pointing to high youth unemployment and real estate issues.
"I don't think it's going to cause China to invade Taiwan. As a matter of fact, the opposite -- it probably doesn't have the same capacity that it had before."
Vietnam has its own squabbles with Beijing, notably over the contested South China Sea.
Hanoi's state media on Monday hailed the deal with former war foe the United States as "historic".
Biden will end his visit by paying his respects at a memorial to his friend John McCain, the former US Senator shot down in Hanoi as a pilot during the Vietnam War.
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