Joe Biden has become the Democratic Party’s presumptive presidential nominee, Sky News’ US partner network NBC News projects.
The sitting president is widely expected to face Mr Trump in the election later this year – a re-run of the 2020 vote.
This will be the first time since 1956 that two presidents will go head-to-head.
And the campaign will almost certainly deepen the nation’s political and cultural divides in the eight-month fight for the White House.
Mr Biden released a statement after clinching the nomination, in which he said: “Voters now have a choice to make about the future of this country.
“Are we going to stand up and defend our democracy or let others tear it down? Will we restore the right to choose and protect our freedoms or let extremists take them away? Will we finally make the wealthy pay their fair share in taxes – or will we allow corporate greed to run rampant on the backs of the middle class?”
NBC News correspondent Mike Memoli said the network projected Mr Biden won the battleground state of Georgia in the primary elections.
He surpassed the “magic number” of 1,968 delegates to secure the nomination.
Memoli said the result was “not a surprise” given the current president was running against “token opposition” – including Californian Governor Gavin Newsom and Michigan Governor Gretchen Whitmer – who sat out rather than challenge Mr Biden who had already beaten his predecessor once before.
Meanwhile, Mr Trump is closing in on the 1,215 delegates needed for the Republican presidential nomination, with contests held in Georgia, Mississippi, Washington and Hawaii on Tuesday.
On Monday, Mr Trump predicted Mr Biden would be the Democratic nominee as he unleashed a new attack on the president’s age.
“I assume he’s going to be the candidate. I’m his only opponent other than life, life itself,” Mr Trump told CNBC.
Mr Biden directed much of his attention toward the former Republican president during a campaign stop in New Hampshire on Monday night.
He described his opponent as a “serious threat to democracy”.
The campaign has not been without difficulties for both frontrunners.
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Mr Trump is facing 91 felony counts in four criminal cases involving his handling of classified documents and his attempt to overturn the 2020 election, among other alleged crimes.
He is also facing increasingly pointed questions about his policy plans and relationships with some of the world’s most dangerous dictators.
And 81-year-old Joe Biden is working to assure a sceptical electorate that he is still physically and mentally able to thrive in the world’s most important job.
He is also dealing with dissent within his party’s progressive base, which is angry he has not done more to stop Israel’s war against Hamas in Gaza.
Mr Biden entered Tuesday 102 delegates short of the 1,968 needed to formally become the presumptive Democratic nominee.
Mr Trump was 137 delegates short of the 1,215 needed to win the Republican nomination at the party’s national convention this summer.