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"No deal means a greater chance of more war in the Middle East," he said.
Obama said the deal is an opportunity worth seizing and warned Congress he would veto any legislation that prevented its successful implementation.
"America negotiated from a position of strength and principle," added Obama, and "stopped the spread of nuclear weapons" in the Middle East.
The "comprehensive, long-term deal," he said, "demonstrated that American diplomacy can bring meaningful change."
If Iran violates the agreement, Obama warned, "the same options available today will be there for future U.S. presidents."
The United States shares concerns raised by Israel and the Gulf states, Obama said, over Iran's support of terrorism and the proxies it supports. However, he added, an Islamic Republic armed with nuclear weapons would be "more dangerous for our friends."
Kerry: U.S. will remain vigilant
U.S. Secretary of State John Kerry also addressed regional concerns over Iran's "destabilizing" activities, stressing that the agreement is solely focused on the "the threat [posed] by Iran's nuclear program."
"The U.S. will continue to support key allies and partners in the Middle East," he said, and remain "vigilant in pushing back against Iran's destabilizing activities."
Kerry also said he did not expect the U.S. Congress to definitively reject the nuclear deal.
Asked what the White House's plan is if Congress rejects the deal with a veto-proof majority, Kerry told reporters: "I really don't believe that people will turn their backs on an agreement which has such extraordinary steps in it with respect to Iran's program as well as access and verification."
Meanwhile, U.S. House Democratic leader Nancy Pelosi said she spoke to Obama on Monday night about the deal and that Congress will scrutinize it.
"Aggressive restrictions and inspections offer the best long-term plan to stop Iran from building a nuclear weapon," Pelosi said in a statement Tuesday. "Congress will closely review the details of this agreement."
Pelosi's support is considered essential to winning enough Democratic support to keep Congress from blocking a deal.
Harry Reid, the U.S. Senate Democratic leader, said on Tuesday the Iran nuclear agreement is the result of years of hard work by Obama and his administration. In a brief statement that did not support or criticize the deal, he said, "Now it is incumbent on Congress to review this agreement with the thoughtful, level-headed process an agreement of this magnitude deserves."
Clinton endorses deal
U.S. Democratic presidential candidate Hillary Clinton called the deal an "important moment" and said based on what she knows, the deal serves as a step toward curbing Iran's nuclear ambitions.
"I think this is an important step that puts the lid on Iran's nuclear programs," the former U.S. secretary of state said. Clinton, speaking at the U.S. Capitol after meeting with House of Representatives Democrats, also said the deal would allow the United States to turn its attention to preventing what it sees as other bad actions by Iran.
Sen. Bernie Sanders (I-Vt.) issued a statement congratulating Obama and Kerry for reaching a deal. "This is a victory for diplomacy over saber-rattling and could keep the United States from being drawn into another never-ending war in the Middle East. I look forward to learning more about the complex details of this agreement to make sure that it is effective and strong.”
Republicans criticize deal
U.S. Senate Majority Leader Mitch McConnell (R-Ky) said the Iran nuclear agreement seemed to retain "flawed" elements of a temporary nuclear deal that has been in place between Tehran and world powers.
But the Senate's top Republican promised a thorough review. "The test of the agreement should be whether it leaves our country and our allies safer," he said in a statement.
U.S. House Speaker John Boehner (R-Ohio) said Obama's nuclear deal with Iran was a "bad deal" that would provide billions of dollars of sanctions relief to Tehran and ultimately allow it to acquire nuclear weapon.
In a news briefing, Boehner insisted he has not prejudged the agreement but told Obama Tuesday morning that he was skeptical of it.
"We're going to do everything we can to get to the details and if in fact it's as bad a deal as I think it is at this moment, we're going to do everything we can to stop it," Boehner told reporters.
The Republican chairman of the U.S. House of Representatives Foreign Affairs Committee criticized the nuclear agreement, saying it does not require Tehran to dismantle bombmaking technology and will allow it to develop an industrialized nuclear program in 10 years.
"The deal they have struck is looking like a tough sell," U.S. Representative Ed Royce, who will convene a hearing on the deal Tuesday morning, said in a statement.
U.S. Republican presidential candidate Marco Rubio said he expected Congress to vote against the Iran nuclear deal, saying the agreement undermines U.S. security.
"I have said from the beginning of this process that I would not support a deal with Iran that allows the mullahs to retain the ability to develop nuclear weapons, threaten Israel, and continue their regional expansionism and support for terrorism," Rubio said in a statement.
"Based on what we know thus far, I believe that this deal undermines our national security."
Fellow Republican presidential contender Mike Huckabee said the Iran deal empowers the Islamic Republic to carry out threats against the United States and Israel.