European nations as well as negotiating partners Russia and China will feel wronged if Congress fails to back President Obama by endorsing the accord, she said.
"They're gonna say, 'we stuck with the Americans, we agreed with the Americans and we hammered out this agreement,'" Clinton said. "And if their president can't make foreign policy that is a very bad signal to send in a quickly moving and often dangerous world."
Her influential former Senate colleague from New York, Sen. Charles E. Schumer, said last week he will oppose the deal, potentially opening the door for other Democrats to defy the White House. Republicans largely oppose the accord, but the White House expects to win some GOP support when Congress considers it next month.
The deal struck in July caps Iran's nuclear abilities but does not guarantee that the Islamic republic can never find a path to a bomb. U.S. ally Israel opposes the deal, which Clinton helped set in motion as secretary of state.
In her most detailed discussion of the deal and the diplomatic run-up to it, Clinton walked a New Hampshire audience through more than five years of back-and-forth with United Nations Security Council members and then with Iran. She suggested that any deal will not be perfect, but said this one is sound.
"You play the hand you're dealt," Clinton said. "And we played that hand to get them to the table to make unprecedented concessions."
Clinton said she would keep working as president to ensure the deal is kept.
"I will do everything necessary to make sure the lid stays on the nuclear weapons program, and I will begin to form a coalition against Iran on all the other things they do which are dangerous," the Democratic front-runner said.