Carter met Israeli Prime Minister Benjamin Netanyahu, a fierce critic of the landmark Iran accord, before flying on to Jordan, a key partner in the US-led war on the Islamic State (IS) group.
Addressing military personnel from six nations in the anti-jihadist coalition at a Jordanian airbase, he said the United States and Israel had a "common commitment to countering Iranian malign influence in the region".
Netanyahu "made it quite clear that he disagreed with us with respect to the nuclear deal and Iran. But friends can disagree," Carter said.
Carter met American forces stationed in Jordan, which shares borders with both Syria and Iraq, as well as colleagues of Jordanian air force pilot Lieutenant Maaz al-Kassasbeh, who was burned alive by IS after his plane crashed in Syria.
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His murder caused global revulsion and vows of international efforts to combat the Sunni Muslim extremist group.
"The enemy has to be defeated," Carter told a small group of US mechanics beside an American F-16 in a hangar at the base.
He later had a private meeting with pilots taking part in anti-IS coalition sorties.
Carter is due in Saudi Arabia tomorrow for a visit expected to be dominated by the kingdom's concerns about the Iran nuclear deal.
Sunni-ruled Gulf countries are wary of the US overtures to arch-foe Iran, believing the nuclear deal will only embolden Tehran's Shiite leaders.
Israel also fears the agreement is not enough to keep the Islamic republic from obtaining nuclear weapons that could be used against it.
Netanyahu has said military force remains on the table to block Iran's path to a nuclear weapon, although experts say unilateral strikes by Israel appear highly unlikely for now.
Carter sought yesterday to address Israeli worries that Washington was shifting its focus in the region, saying Israel remained "the bedrock of American strategy in the Middle East".