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Supreme Leader Ayatollah Ali Khamenei said has said that Iranian opposition to the "arrogant" United States will not change despite a nuclear deal with world powers,
He added that Tehran remains sharply at odds with US policy in the Middle East.
Khamenei made the comments in an address marking the end of the Muslim holy month of Ramadan.
He said politicians should examine the agreement to ensure national interests were preserved, as Iran would not allow the disruption of its revolutionary principles or defensive abilities. American leaders sought Iran's "surrender", he said. Iran would not welcome war but if there were one, the United States would be humiliated.
Iran's Supreme Leader has given a cautious welcome to the country's historic nuclear deal, but warned the text should be "carefully scrutinised" and claiming some of the other nations involved are "not trustworthy".
In a letter - his first public statement on the agreement - he thanked President Hassan Rouhani for the "significant step", but warned: "The text of the deal should be carefully scrutinised and the legal procedures should be taken so when the deal is ratified the other side cannot breach it."
Under the deal, sanctions will be lifted on Iran in exchange for an agreement of long-term curbs on its nuclear programme.
Khamenei is the ultimate authority on all matters of state, but was not directly involved the negotiations.
The P+1 nations that agreed the deal with Iran are China, France, Russia, the United Kingdom and the United States.
Israel is not in favour of the nuclear deal agreed between Iran and other major global powers, Defence Secretary Philip Hammond.
He has said that the country would prefer a permanent stand-off.
"The world can be reassured all Iranian routes to the nuclear bomb have been closed off," according to the foreign secretary Philip Hammond.
The UK also plans to re-open an embassy in Iran once confidence in its nuclear ambitions has been restored.
As part of the deal, global economic sanctions on Iran are also set to be relaxed in stages.
Iranians took to the streets of Iran this evening to celebrate after the country signed an historic deal to lift sanctions in exchange for halting its nuclear programme.
In the more affluent north of the capital, young crowds chanted and clapped, while some held aloft pictures of Iranian foreign minister Mohammad Javad Zarif and President Hassan Rouhani.
One person, a university student said: "I feel a little lighter from all that tough work. Thank you Dr. Rouhani and thank you Dr. Zarif."
The deal is set to end years of economic hardship for Iran, which over the past three years has been stripped of access to the international financial system, making it hard to sell oil and pay for imports.
Today's nuclear deal with Iran will be "centre stage" in Barack Obama's legacy as President, ITV News International Affairs Editor Rageh Omaar says.
In his video blog, Omaar says the agreement is the first international deal of its kind to have been "personally driven" by a US President since Jimmy Carter helped broker the Camp David Accords between Egypt and Israel in the 1970s.
Despite likely opposition from the Republican-led Congress, Omaar says the President will use his veto to pass the deal into law.
He adds, however: "The question is, will it out-survive whoever becomes the next President of the United States in November 2016?"
The deal agreed between Iran and the P5+1 negotiating powers limits Iran's nuclear programme in return for the lifting of sanctions.
The Joint Comprehensive Plan of Action runs to more than 80 pages and full details are still emerging, but so far we know that as a result of the deal:
- Iran has affirmed that under "no circumstance" will it seek to develop nuclear weapons
- Tehran will place thousands of its nuclear centrifuges into monitored storage
- UN inspectors will be allowed extensive access to Iranian military sites
- An arms embargo against Iran is to remain in place for five years
- Sanctions against Iran's ballistic missile programme will remain in place for eight years
- Sanctions will 'snap-back' in place after 65 days if Iran does not comply with its obligations under the deal
Negotiators have reached an agreement on Iran's nuclear programme that will limit Tehran's ability to develop nuclear weapons in return for the lifting of sanctions.
The deal was announced in Vienna by Federica Mogherini, the EU's foreign policy chief, and Mohammad Javad Zarif, the Iranian foreign minister.
It ends 20 months of negotiations between Iran and six world power.
While the deal was welcomed by its negotiators, Israel's prime minister was quick to call it "a bad mistake of historic proportions".
Hassan Rouhani, the Iranian president, has welcomed the nuclear deal struck between his country and the six negotiating world powers, and urged regional neighbours to ignore Israeli "propaganda" about the deal.
He said the "win-win" deal would begin a new chapter of cooperation with the outside world after years of sanctions.
He said that Iran had a shared interest with its neighbours in the stability of the region and would abide by its commitments under the deal, as long as the other powers also did so.
The nuclear deal is a considerable triumph for Rouhani who has had to combat conservative factions at home while his foreign minister Mohammad Javad Zarif engaged in negotiations abroad.
The 66-year-old cleric had to keep up domestic support for an agreement and convince all sectors of Iranian society that it was in their interests.
Prime Minister David Cameron has hailed the international community's deal with Iran as "historic", saying it will "keep Iran from developing a nuclear weapon and help to make our world a safer place".
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Prime minister Netanyahu has likened the nuclear deal with Iran to the unsuccessful 1994 deal on North Korea's nuclear programme.
An end to Iranian nuclear question could soon be a reality after years of hard and often tense negotiations.