Every Senate Republican opposed the vote to start debate on the voting rights bill.
"This bill is a compromise, but a good one. It's a bill that every Senate Democrat is united behind enthusiastically," said Senate Majority Leader Chuck Schumer before the vote. Schumer had worked to get moderate Democrat Joe Manchin behind the proposal known as the Freedom to Vote Act.
Manchin, D-W.Va., refused to endorse a more comprehensive reform effort by his caucus in June, saying it lacked bipartisan input and encroached too far on state's rights to run elections. But after months of trying to corral GOP support, Manchin has found none.
The vote on Wednesday was to start debate on the measure, a move that required 10 Republicans to vote with all Democrats. But no Republicans supported the revised bill.
"There are areas where we could perhaps work together, but the legislation that's been crafted (by Democrats) is not what I'll support," said Sen. Mitt Romney, R-Utah, a consensus-minded Republican whom Manchin approached. "Federalizing election law is something which I think is not a good idea."
Sen. Angus King, D-Maine, a lead sponsor of the legislation and member of that working group, pleaded with colleagues to support the bill, saying U.S. democracy is "fragile" and at stake in the wake of Trump's false claims about the 2020 election despite no widespread fraud found in multiple, nonpartisan investigations.
"The problem with this goes well beyond the wave of voter suppression legislation sweeping the country; the deeper problem is the massive and unprecedented erosion of trust in the electoral system itself, the beating heart of our democracy," said King. "Of all the depredations of Donald Trump, this is by far the worst. In relentlessly pursuing his narrow self-interest, he has grievously wounded democracy itself. And by the way, I mean 'narrow self-interest' quite literally; he doesn't give the slightest damn about any of us -- any of you -- and will cast any or all of us aside whenever it suits his needs of the moment."
But Republicans for months have said they see the efforts to counter red state laws as nothing more than "a partisan power grab."
"The only thing this proposal would have done for the people…would be to help make sure that the outcome of virtually every future election meant that Democrats win and Republicans lose. Thus, Republicans would be relegated to a permanent minority status. That was the goal," Sen. John Cornyn, R-Texas, charged in a Tuesday floor speech. "If this bill weren't so dangerous, it would have been laughable."
King told reporters on a conference call that the only option after the vote Wednesday is to alter the Senate's filibuster rule that requires 60 votes to pass most legislation but also imposes no requirement on the 41 senators who are in opposition other than his or her stated opposition to legislation that is up for a vote.
"I've been very, very reluctant on (changing the filibuster), but on the other hand, it strikes me that this is a very special case, because it goes to the very fundamentals of how our democracy works," King told reporters, adding that the debate among Democrats "can't go on forever, because as you know redistricting has already started in states…It's got to happen, I would say, in this calendar year."
King said Democrats are looking at a number of possible changes, from requiring those supporting a filibuster to appear on the floor and hold the chamber with speeches -- the so-called "talking filibuster" -- to modifying the rules to end filibusters on motions to start debate -- which is what will happen Wednesday -- to ending the filibuster altogether.
Changing the filibuster would require all Democrats to be united, but that is not the case currently. Manchin and his fellow moderate, Kyrsten Sinema of Arizona, have steadfastly refused to change the chamber's rules citing a fear of permanently damaging the institution.
Outside groups pushed back Tuesday and called on Biden to do more.
"The president must get in the game. Say into a microphone, 'You've got to get rid of the filibuster," said Meagan Hatcher-Mays of the progressive group Indivisible.
"The filibuster is paralyzing the Senate. It's preventing it from doing the very basics, such as debating bills," said Adam Jentleson, a one-time deputy chief of staff to former Senate Majority Leader Harry Reid, D-Nev., and founder of the Battle Born Collective, a progressive interest group.
White House press secretary Jen Psaki demurred Tuesday when asked about support for the filibuster.
"It's a discussion that we would have with leaders and members in Congress," said Psaki, who added that the White House was focused on the Wednesday vote. "Republicans still have an opportunity to do the right thing to protect people's fundamental right to vote."
The Democrats' new bill still encompassed sweeping election law changes, including voter ID requirements, expanded early voting, making Election Day a national holiday, banning partisan gerrymandering, and implementing election security and campaign finance measures.
Among the provisions dropped or changed since June were the automatic mailing of ballots. Under the new measure, any voter could request a mail-in ballot but they are not sent out automatically. The legislation would have continued to allow voter roll purges but required changes to be "done on the basis of reliable and objective evidence" and prohibited the use of returned mail sent by third parties to remove voters.
The bill would have also no longer implemented public financing of presidential and congressional elections. Still, there were a number of election security provisions, including mandatory, nationwide use of machines that deliver paper ballots.
ABC News' Allie Pecorin contributed to this report.