President Obama scored a major foreign policy victory Wednesday after securing enough votes in the Senate to preserve the nuclear deal with Iran, which has come under intense criticism from Republicans and some Democrats.

The agreement to curb Iran’s nuclear ambitions, struck by international negotiators in Vienna in July, was the subject of an intense lobbying campaign in recent weeks by both the administration and the deal’s opponents in advance of an expected vote as early as next week on a resolution to block the deal’s implementation.

Sen. Barbara A. Mikulski (D-Md.) on Wednesday morning said she will back the agreement, making her the 34th senator to pledge support for the Iran deal in the Senate. This means that opponents will not be able to collect the two-thirds supermajority vote needed to override Obama’s promised veto of any legislative attempt to dismantle the nuclear pact.

“No deal is perfect, especially one negotiated with the Iranian regime. I have concluded that this Joint Comprehensive Plan of Action is the best option available to block Iran from having a nuclear bomb,” Mikulski said in a statement explaining her decision.

In recent weeks, all eyes have been focused on about a dozen undecided senators — including Mikulski — whose votes were seen as potentially making or breaking the deal.  The pressure on those lawmakers has been intense, as the deal’s champions and detractors have wielded everything from entreaties to campaign threats in trying to win their votes.

The announcement by Mikulski, who is retiring at the end of next year and does not need to worry about political blowback, gives her still-undeclared colleagues cover to state their positions without worrying about the responsibility – or political fallout – of becoming the senator to clinch the deal.

Congress secured an unorthodox role for itself in the negotiations earlier this year by passing legislation demanding a chance for lawmakers to review the accord that the United States, Russia, China, Britain, France and Germany were negotiating with Iran to rein in Tehran’s nuclear development program. The deal they struck trades promises from Iran to mothball centrifuges, cut enriched-uranium stockpiles and accept tight oversight in exchange for a stage-by-stage lifting of sanctions that have hamstrung the Iranian economy.

The president’s win is stinging defeat for the lobbying groups and lawmakers opposing the deal, who spent countless hours and millions of dollars to block its implementation.

Since the agreement was reached in July, they have complained that it doesn’t do enough to prevent Iran from getting a nuclear weapon and, at best, only delays its pathway to becoming an armed nuclear state. Even those on the fence have openly worried that Iran might funnel some of the money that gets pumped back into its economy after sanctions are lifted into nefarious activities, including funding groups that pose a direct threat to Israel.

“The only reason the Ayatollah and his henchmen aren’t dancing in the streets of Tehran is they don’t believe in dancing,” Sen. Lindsey O. Graham (R-S.C.), who is also running for president, said following Mikulski’s announcement.

The deal’s detractors also painted the move as dangerous for Israel and Israeli news media reported Mikulski’s declaration as a clear loss for Israeli Prime Minister Benjamin Netanyahu, who has spent years warning that a nuclear Iran poses an existential threat to Israel. Earlier this year he took the extraordinary step of siding with Republicans and directly confronting the Obama in a speech before Congress.

But Obama and his proxies have argued that the deal is the best agreement they could have secured, that there is no alternative to it but war with Iran and that those angling to rip up the current deal and call Iran back to the negotiating table do not have a viable alternative.

Secretary of State John F. Kerry stressed these points and responded to criticism of the deal in letters he sent to the Senate and House Wednesday, in which he called Israel’s security “sacrosanct” and noted that the United States and Israel were working out a memorandum of understanding to “cement for the next decade” what he called “unprecedented levels of military assistance.” That assistance is expected to include advanced F-35 fighter aircraft, funding to develop newer systems like the Arrow-3 and David’s Sling and efforts to identify and destroy tunnels that could be used in efforts to harm Israeli citizens. Obama and Netanyahu have already spoken about countering threats to Israel, Kerry noted.

WATCH: Secretary of State John Kerry has harsh words for the Iran nuclear deal oppososition (AP)

“President Obama and this Administration firmly believe we have an opportunity now to build on and fortify the United States’ historic and enduring commitment to Israel’s security,” he wrote.

Kerry’s letters were delivered as he made a speech in Philadelphia that was broadcast live on Iranian television.

“Rejecting this agreement would not be sending a signal of resolve to Iran, it would be broadcasting a message so puzzling that most people across the globe would find it impossible to comprehend,” Kerry said in his speech at the National Constitution Center.

“It’s hard to conceive of a quicker or more self-destructive blow to our nation’s credibility and leadership,” he added, “not only with respect to this one issue, but across the board, economically, politically, militarily, even morally. We would pay an immeasurable price for this unilateral reversal.”

In Israel, the immediate reaction was muted.

One senior Israeli official close to Netanyahu said, “Whatever is going on in Congress does not change the dangers facing the Middle East from the agreement as it has been currently presented.”

The official said that Israel never said it would win its case, but that it was important to make one.

A second Israel official indicated Netanyahu will keep attacking the deal.

“The Prime Minister has a responsibility to point out the flaws of an agreement that endangers Israel, the region and the world — and he will continue to do so,” they said. “He believes the deal is a mistake.”

The White House declined to take a victory lap before the vote actually occurs. Josh Earnest, Obama’s spokesman, said the focus is on winning over as many lawmakers as possible.

“Every vote is important,” he told reporters during the president’s trip in Alaska.

Along with Israeli officials, other deal opponents, such as the American Israel Public Affairs Committee (AIPAC), are refusing to label the Iran vote a defeat, while promising to continue to press their case.

They are working on the remaining undecided senators to try and ensure that as few lawmakers as possible support the Iran deal – even if Obama’s veto of a disapproval resolution is now sure to be upheld.

Now that the veto-sustaining 34th vote in favor of the deal has been pledged, the question is not whether the Iran deal will survive its congressional test, but how. Ten Democrats remain undeclared, and if just seven more of those senators vote for the deal, Obama’s supporters will number 41 – enough to sustain a filibuster against a resolution of disapproval, meaning the president might not need to use his veto pen.

Republican leaders, like Senate Foreign Relations Chairman Bob Corker (R-Tenn.), are crying foul over the possibility of a filibuster, arguing an up and down vote is justified on an issue as important as Iran’s nuclear ambitions.

“While the President may be able to sustain a veto with the tepid, restricted and partisan support of one third of one House of Congress over Americans’ bipartisan opposition, it will require a bipartisan Congress to strengthen our defenses in the Persian Gulf and to stand up to the inevitable Iranian violations of the agreement that will need to be addressed after he has left office,” Senate Majority Leader Mitch McConnell (R-Ky.) said in a statement.

William Booth and Kelsey Snell contributed to this story