The decision by the influential Jewish lawmaker was quickly matched by another leading Democrat, Eliot Engel, the ranking Democrat on the House foreign affairs committee.
"Advocates on both sides have strong cases for their point of view that cannot simply be dismissed," Schumer, the number three Democrat in the Senate, said in a statement yesterday.
"This has made evaluating the agreement a difficult and deliberate endeavor," he admitted, following days of speculation about his intentions.
Separately, Engel said that he simply did not trust Iran to uphold its end of the agreement to curtail its nuclear program in exchange for an easing of crippling economic sanctions.
"I still believe that a negotiated solution is the best course of action. That's the path I believe we should pursue. But ... I regret that I cannot support this deal," he said.
The announcements were a serious blow to Obama, who is in the midst of an intense lobbying effort to get Congress to back his landmark agreement, arguing that to torpedo it would be to risk a wider Middle East war.
Obama will veto that measure, but Congress could override such a veto - and kill the Iran deal - with a two-thirds majority in both the Senate and House of Representatives.
House Democratic leader Nancy Pelosi is said to be assembling a team aimed at securing the necessary votes to uphold the veto.
But earlier this week House Democrat Steve Israel - like Schumer a major Jewish voice in Congress - came out against the deal.
In his statement, Schumer insisted he would vote against the accord "not because I believe war is a viable or desirable option" but because Iran will continue to pursue its "nefarious goals."
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