Sen. Joe Manchin (D-W.Va.) on Capitol Hill in November 2014. Manchin said Tuesday he will oppose the Iran nuclear deal, breaking with his party. (Carolyn Kaster/AP)

Three Democratic senators announced Tuesday they will vote in support of the nuclear deal with Iran, paving the way for a possible filibuster of Republican-led attempts to disapprove of the controversial agreement.

Pro-deal statements from Sens. Richard Blumenthal (D-Conn.), Gary Peters (D-Mich.) and Ron Wyden (D-Ore.) mean 41 senators are now publicly backing the deal, enough to keep a disapproval resolution from emerging from the Senate and making its way to President Obama's desk and forcing a veto.

A fourth Democrat making an announcement Tuesday, Joe Manchin (D-W.Va.), said he would vote to disapprove of the deal, as did the last undecided Republican, Susan Collins of Maine, thus dashing White House hopes for bipartisan Senate support.

The decisions come on the day lawmakers are reassembling after a month-long break, with the Iran deal at the top of a high-stakes list of September business. Six Democrats remained undecided at the close of the holiday weekend. With 38 senators already publicly in favor of the deal — enough to sustain a presidential veto — none of those senators was expected to derail it. But the question of whether Democrats would cobble together enough support to prevent a disapproval resolution from reaching Obama's desk has been closely watched on Capitol Hill.

[The Iran deal is unpopular. Here’s how it could hurt Democrats.]

The prospect of a filibuster prompted sparring between the party floor leaders Tuesday afternoon, minutes after the Senate gaveled back to business. Majority Leader Mitch McConnell (R-Ky.) took aim at Democrats, saying senators "should not hide behind procedural obfuscation to shield the president or our individual views" — arguing that the Iran disapproval should live or die on a vote for final passage, not on a procedural vote requiring 60 senators.

But Minority Leader Harry M. Reid (D-Nev.) cited multiple occasions where McConnell threw up procedural roadblocks when Republicans were in the minority: "After the numerous speeches that he has given about the 60-vote threshold on everything important, is he suggesting this Iran agreement is not important?" Reid asked.

At the White House, press secretary Josh Earnest said the administration felt "gratified" by the growing support for the Iran nuclear deal, and he suggested that the White House expects Senate Democrats to lead a filibuster of disapproval legislation.

Supporters "should take the necessary steps in Congress to prevent Congress from undermining the agreement," Earnest said. Like Reid, he noted that Republicans often filibustered legislation when the GOP was in the minority in the Senate.

Blumenthal, Peters and Wyden had long been considered possible opponents of the deal, given the opposition of the Israeli government and significant elements of the American Jewish community. Blumenthal and Wyden are Jewish, and Peters has close ties to Michigan's Jewish leadership; all have made comments critical of the deal since its announcement in July.

But all three said in separate statements Tuesday that the deal negotiated by President Obama in conjunction with international allies is, while imperfect, the best path forward.

“While this is not the agreement I would have accepted at the negotiating table, it is better than no deal at all," Blumenthal said.

"This agreement with the duplicitous and untrustworthy Iranian regime falls short of what I had envisioned, however I have decided the alternatives are even more dangerous," Wyden wrote.

Peters said, "Despite my serious concerns with this agreement, I have unfortunately become convinced that we are faced with no viable alternative."

Manchin is the fourth Senate Democrat to oppose the deal, following Charles E. Schumer (N.Y.), Robert Menendez (N.J.) and Ben Cardin (Md.). One senator, Maria Cantwell (Wash.), has not yet announced her position.

Manchin said in a statement that he "could not ignore the fact that Iran, the country that will benefit most from sanctions being lifted, refuses to change its 36-year history of sponsoring terrorism. ... I cannot gamble our security, and that of our allies, on the hope that Iran will conduct themselves differently than it has for the last 36 years."

He added that if Iran is caught violating the nuclear agreement, "I have grave doubts that we will have unified, committed partners willing to prevent Iran from obtaining a nuclear weapon."

Congress faces a tight timeline for taking action on the Iran deal. Under review legislation passed earlier this year, lawmakers have until Sept. 17 to weigh in for or against the agreement. McConnell on Tuesday, after sparring with Reid, made procedural moves to limit floor amendments in order to speed consideration of a disapproval bill. Initial votes could come as soon as Thursday.

McConnell said last month that he expects to have a debate beforehand "with the dignity and respect that it deserves" -- including the rare spectacle of having all 100 senators at their desks on the floor. On Tuesday he asked all senators to be present in the Senate chamber starting Wednesday afternoon.

Reid (D-Nev.) on Tuesday defended the deal in a morning address at the Carnegie Endowment for International Peace in Washington and laid out some of the procedural hurdles to be dealt with in the coming days. Democrats have already passed up one opportunity to bottle up the Iran opposition by agreeing to begin debate on the deal. But it will take 60 votes to close debate and quickly move to a final vote.

Senate Minority Leader Harry Reid (D-Nev.) defended the nuclear deal with Iran, saying Democrats have enough votes in the Senate to ensure the deal isn't blocked. (AP)

“There is no precedent in recent history for an issue of this magnitude getting consideration in the Senate without having to secure 60 votes," Reid said. "This is not about how any one leader manages the floor – this is a precedent stretching back decades."

Manchin's decision to oppose the deal stands as one of the few clear-cut victories for the anti-deal forces that had hoped to swing lawmakers' opinion during the August summer break, spending millions on TV and radio ads. Before leaving Washington, Manchin had indicated he was "leaning very strongly" in support of the agreement, as he put it in a July 26 appearance on CBS's "Face the Nation."

But public opinion in West Virginia, whose politics have trended increasingly conservative over the past two decades, was strongly against the deal, and Manchin undertook an unusually public deliberative process. On his Web site, he listed dozens of meetings, hearings and briefings he had participated in with key policymakers inside and outside the federal government. And he was virtually the only decided Democrat to take his decision directly to his constituents by holding town hall meetings in his home state.

[West Virginia is getting an up-close look at one undecided Democrat’s Iran agony]

About 500 attended a Thursday town hall in Charleston, and the opinions of those attendees ran strongly against the agreement. Many wore shirts declaring, "We Need a Better Deal." During the event, Manchin declared himself undecided, gave numerous facts and arguments both for and against the deal, and said whatever decision he made would be a close call.

"If anyone tells you they are 100 percent for this deal or 100 percent against this deal, they haven't read it," he said. "They haven't studied it. The best I could ever could be is 60 percent for, 60 percent against, and it'll probably come down, it'll be 51 percent for or against when I make the final decision."

Karoun Demirjian and David Nakamura contributed to this report.