US networks predicted that Sanders, a self-described democratic socialist on a mission to reshape America's economy, would win as expected in Vermont.
However, the 77-year-old centrist Biden looked set to take the far bigger and more diverse Virginia, where polls also closed at 7:00 pm (0000 GMT Wednesday).
From there, the action was to pick up speed, with polls closing across a slew of states in the following hours, before culminating in delegate-rich California at 11:00 pm (0400 GMT).
The nominating contests across the country give the dwindling field of Democratic hopefuls a giant potential haul of delegates in their bid to win the nomination -- and begin campaigning in earnest against the Republican incumbent.
Many in the Democratic Party are desperate to stop Sanders' strong showing in the delegate race, saying the senator will be destroyed in a general election where Trump has signaled he will brand him a socialist bent on ending the American way of life.
Biden, counted out after a stumbling early campaign, suddenly rebounded with a landslide win in South Carolina a few days ago, followed by the coordinated decisions by two moderate candidates -- Pete Buttigieg and Amy Klobuchar -- to withdraw and endorse their former rival.
But Sanders' enthusiastic base is convinced only he can take on Trump, who also defied his party's establishment and more moderate wing four years ago to claim a surprise victory against Democratic heavyweight Hillary Clinton.
"We need energy. We need excitement. I think our campaign is that campaign," said the 78-year-old Sanders.
Sanders supporter Jamison Hanning, a 45-year-old plastics industry technician, said he was "pretty confident" despite the Biden pushback.
"I mean it is just people in the establishment being afraid of things being shaken up," he said.
Former New York mayor Michael Bloomberg and Massachusetts Senator Elizabeth Warren were also on the ballot.
Trump, who feels confident with a strong economy and the benefit of having campaigned for re-election since the day he took office, said he would be watching closely.
"It's going to be a very interesting evening of television. It's going to really be something," he said.
Asked whom he wanted to face, he answered: "Anybody."
Two new national polls have shown Biden surging past Sanders.
'We're in it to win it'
Bloomberg, 78, who has poured hundreds of millions of dollars of his own money into the race but is not expected to win any states on Tuesday, rejected calls to follow Buttigieg and Klobuchar, clearing a path for Biden.
"I have no intention of dropping out," the billionaire told reporters in Florida. "We're in it to win it."
After disappointing finishes in the first three contests, Biden righted his listing campaign in South Carolina and is hoping the energy from that victory carries over into Tuesday's contests.
A total of 1,357 delegates are at stake, and Biden needs another good performance to prevent Sanders from taking a potentially insurmountable lead into the party convention to be held in Milwaukee in July.
A candidate needs 1,991 delegates to win the nomination outright and Bloomberg acknowledged his only hope may be a contested convention, where no single candidate arrives with the delegates needed to win on the first ballot.
No 'revolution'
Biden, who is making his third bid for the White House after failed runs in 1988 and 2008, appears reinvigorated by his recent successes and compared Buttigieg, 38, to his own son Beau, who died of brain cancer in 2015.
"The fact that he's prepared to help me means a great deal to me," Biden said.
"I don't think I've ever done this before, but he reminds me of my son Beau."
Biden also sought to warn voters away from Sanders.
"Most Americans don't want the promise of a revolution," Biden said. "They want results. They want a revival of decency, honor and character."
The endorsements could be the start of Biden's last hope to seize the initiative.
But Democrats will also be looking for turnout and other signs of enthusiasm in a country deeply divided by Trump.
California voter Brian Waters, 43, a former English teacher who is now a brewer, said he voted for Sanders because of his position on universal health care.
But he added: "I'd vote for a burning dumpster over Trump."
