WASHINGTON — Officials at the American Israel Public Affairs Committee knew the odds were against them in the fight to block President Obama’s nuclear deal with Iran from surviving a congressional vote. But the influential pro-Israel group threw itself into a nearly $30 million advertising and lobbying effort to kill the accord anyway.

On Thursday, the committee, known as Aipac, was handed a stinging defeat. After Mr. Obama mustered enough Democratic backing in the Senate to halt a vote on a resolution of disapproval against the deal, a group known for its political clout saw its power and reputation in Washington diminished.

“They failed — they couldn’t even get a vote,” said Clifford Kupchan, an Iran expert and the chairman of the Eurasia Group, a consulting firm, who noted that Aipac had gone “all in” and tried everything to stop the deal. “It’s among the biggest setbacks for Aipac in recent memory.”

The loss has raised difficult questions about the future of Aipac, a group formed in 1951 just a few years after the birth of Israel. Aipac has long drawn its political potency from its reservoirs of loyalty among members of both parties, but that bipartisan veneer all but vanished in recent weeks as the debate over the Iran deal became increasingly bitter.