Biden will address the assembly in-person tomorrow and then go back to Washington where he'll continue to engage with fellow world leaders virtually.
It will be a departure from the last in-person meeting of the General Assembly in 2019 - and far different, too, from last year's all-virtual version.
But COVID concerns will still loom over the high-profile event after the White House expressed fear the General Assembly could be a 'superspreader event.'
Awaiting world leaders are daunting challenges, from an escalating climate crisis and severe COVID vaccine inequities to Afghanistan´s future under its new Taliban rulers and worsening conflicts in Myanmar and the Tigray region of Ethiopia.
Secretary-General Guterres keeps repeating that the world is at 'a pivotal moment' and must shift gears to 'a greener and safer world.'
To do that, leaders need to give multilateralism 'teeth,' starting with joint action to reverse the global failure to tackle COVID-19 in 2020 and to ensure that 70 percent of the world´s population is vaccinated in the first half of 2022.
Biden will fly to New York City on Monday afternoon where he will meet with the U.N. Secretary-General before addressing world leaders at the General Assembly the next day
Biden, meanwhile, will face questions on his day-one promises that the erratic policy decisions of the Trump administration are behind him.
On Tuesday he'll try to make the case to allies that 'America is back' and willing to lead on global challenges like climate change, human rights and the coronavirus pandemic.
Biden's chief envoy to the United Nations, Ambassador Linda Thomas-Greenfield, offered a harmonious answer in advance of all the diplomacy: 'We believe our priorities are not just American priorities, they are global priorities,' she said Friday.
At a virtual COVID-19 summit he is hosting Wednesday, leaders will be urged to step up vaccine-sharing commitments, address oxygen shortages around the globe and deal with other critical pandemic-related issues.
The president also has invited the prime ministers of Australia, India and Japan, part of a Pacific alliance, to Washington and is expected to meet with British Prime Minister Boris Johnson at the White House.
But over the past several months, Biden has found himself at odds with allies on a number of high-profile issues.
Secretary-General Antonio Guterres warned heads of state that the world is at a 'pivotal moment' right now
There have been noted differences over the U.S. withdrawal from Afghanistan, the pace of COVID-19 vaccine-sharing and international travel restrictions, and the best way to respond to military and economic moves by China.
A fierce French backlash erupted in recent days after the U.S. and Britain announced they would help equip Australia with nuclear-powered submarines.
But Biden and European allies have also been out of sync on other matters, including how quickly wealthy nations should share their coronavirus vaccine stockpiles with poorer nations.
Early on, Biden resisted calls to immediately begin donating 4 percent to 5 percent of stockpiles to developing nations.
In June, the White House instead announced it was buying 500 million doses to be distributed by a World Health Organization-backed initiative to share vaccine with low- and middle-income countries around the globe.
Biden is soon expected to announce additional steps to help vaccinate the world.
Allies among the Group of Seven major industrial nations have shown differing levels of comfort with Biden’s calls to persuade fellow democratic leaders to present a more unified front to compete economically with Beijing.
When the leaders met this year in England, they agreed to work toward competing against China. But there was less unity on how adversarial a public position the group should take.