The Republican-controlled Congress is expected to pass a measure disapproving of the deal, which Obama has pledged to veto. And despite Schumer's move, both the administration and congressional Democrats supporting the Iran deal remain confident they have the votes to sustain the veto. They're looking to the House of Representatives as the firewall to ensure the nuclear agreement can be implemented.
Schumer's opposition was expected by Obama administration officials and most members of his party on Capitol Hill even if it's fueling speculation that his prospects to become the next Senate Democratic leader could be damaged.
"Not particularly surprising to anybody here at the White House," White House Press Secretary Josh Earnest said about Schumer's decision to come out as a "no" vote, which he announced late Thursday.
Most Democrats understood the enormous political pressures Schumer, the highest-ranking Jewish lawmaker in Congress, felt from powerful interests in his home state, and say his longstanding positions on Mideast foreign policy made it a good bet he couldn't back the deal.
But they also believed he would lay low and wait until shortly before the vote to publicly split with the administration. It was Schumer's post on Medium giving a laundry list of reasons he thinks the deal has "serious weaknesses" that caught many Democrats off guard. And some say with several weeks left before the vote that lengthy analysis of what he views as the deal's flaws could prove influential among undecided Democrats.
"There is no denying that he was the one of the largest fish in the pool, which is why so much attention was centered on him from the very beginning," one senior House Democratic source told CNN.
In recent weeks, Schumer had individual meetings with Obama, Secretary of State John Kerry and lead negotiator Wendy Sherman. He also had dinner with Kerry, Sherman and Energy Secretary Ernest Moinz.
Given his decision, U.S. officials have complained that it's unclear where all that work went, especially since they believe Schumer's statement didn't reflect the substance of those conversations, either about the deal itself or the consequences if Congress were to vote it down.
Now that Schumer's opposition is public, the big question is how actively he will lobby others to join him and vote to reject the deal.
According to multiple Democratic aides, Schumer spent Friday making calls to Senate colleagues and House Democrats from the New York delegation to tell them why he decided to oppose the deal. He also called the White House to let them know in advance of making his views public. Schumer planned to make calls to fellow Democratic members ahead of making his position public, but after the news was leaked late on Thursday he didn't get the chance to give members a heads up.
Schumer insists that he is not twisting arms.
"There are some who believe that I can force my colleagues to vote my way. While I will certainly share my view and try to persuade them that the vote to disapprove is the right one, in my experience with matters of conscience and great consequence like this, each member ultimately comes to their own conclusion," Schumer said in a written statement on Friday.
Other Democratic congressional sources aren't convinced he won't use some political pressure to push those on the fence over to his side, and say he will be closely watched in the coming weeks.
Despite the high profile break with Schumer, the math to get votes to override the president's veto favors the administration at this point.
The White House needs one chamber to sustain the veto and procedurally, the first vote would be in the House, where Minority Leader Nancy Pelosi, D-California, was an early supporter of the deal. She is a skilled vote counter and has worked diligently to move her caucus to support the President. Pelosi's close coordination with the administration may also be a way for her to redeem herself after her own high profile split with the president on his trade bill earlier this summer.
Multiple House Democratic leadership aides continue to express confidence they have the votes. If all Republicans vote to override, they would need 44 House Democrats to join them to block the agreement. At this point, there are nine House Democrats who are publicly opposed.
House supporters also point to a letter signed by 151 House Democrats in May backing the administration's negotiations with Iran on the nuclear deal. While the letter wasn't an explicit endorsement of the deal unveiled last month, none of the members who signed onto that letter have publicly opposed the deal yet.
In the Senate, where Schumer's voice is more influential, Republicans need to lock down 60 votes to clear a procedural vote to bring up a GOP resolution of disapproval. Schumer and New Jersey Democratic Senator Bob Menendez, who has been critical, are expected to vote with the 54 Senate Republicans likely to stand united against the deal, but that is still leaves the GOP four votes short of overcoming a Democratic filibuster.
Even if opponents get the votes to pass the resolution of disapproval in the Senate, they still need a total of 13 to block the nuclear deal. The No. 2 Senate Democrat, Dick Durbin of Illinois, is helping the administration round up votes, and several Democrats who were mum until recently, including Schumer's junior senator, Kirsten Gillibrand, and Wisconsin Sen. Tammy Baldwin, now say they will support the deal.
The remaining undecided Senate Democrats include Ben Cardin of Maryland, the top Democrat on the Senate Foreign Relations Committee, and Cory Booker of New Jersey. Both potentially face similar political pressures as Schumer from Jewish groups in their states who want the deal to fall apart.
Others who say they are still evaluating the agreement include Senators Richard Blumenthal of Connecticut, Mark Warner of Virginia, Chris Coons of Delaware, Debbie Stabenow of Michigan, Gary Peters of Michigan, Joe Donnelly of Indiana, Jon Tester of Montana, Claire McCaskill of Missouri and Heidi Heitkamp of North Dakota. Senate Democratic Leader Harry Reid continues to say he is also reviewing the details of the Iran deal, but he is retiring and most expect he will support the White House.