Tehran and six world powers, including the United States, agreed to the deal in July when Iran promised to scale down its nuclear activities in return for the lifting of painful UN and Western sanctions, including on its lifeblood oil exports.
"The incentives are aligned for Iran to uphold its side of the deal. We're watching Iran like a hawk," Biden said.
"Under this deal, Iran would never be allowed to pursue nuclear weapons, never, never, never," he told the annual policy conference of the American Israel Public Affairs Committee (AIPAC) lobby group.
Iran has denied wanting nuclear weapons, saying its nuclear activities were exclusively for peaceful purposes such as power generation.
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Under the deal the lifting of the nuclear sanctions takes place progressively in line with Tehran meeting its commitments.
A key provision allows the sanctions to be restored or "snap-back" immediately if Iran is found in breach of the agreement.
Yet in Israel -- where many fear being targeted by Tehran -- there are still widespread concerns about security in the wake of the agreement.
On the issue of US military aid for Israel, Biden vowed forthcoming assistance would be "without a doubt the most generous security package in the history of the Unites States.