Days after the United States widened bombing raids against jihadists in Iraq to Syria, Rouhani warned that regional moderates -- albeit with international support -- were best placed to resolve extremism threatening the world.
"The strategic blunders of the West in the Middle East, Central Asia and the Caucasus have turned these parts of the world into a haven for terrorists and extremists," he told the UN General Assembly in New York.
"Improper interference in the developments in Syria are clear examples of this erroneous strategic approach in the Middle East."
The United States has the support of five Arab countries in its air campaign to defeat what President Barack Obama on Wednesday called a "network of death" -- the Islamic State group.
"The right solution to this quandary comes from within the region... with international support and not from outside," he said, warning otherwise there would be "repercussions for the whole world."
There was no interaction between Obama and Rouhani on the sidelines of the General Assembly, Deputy National Security Advisor Ben Rhodes told reporters.
The two leaders last year spoke by telephone, but expectations had been low of contact this time.
Rouhani is determined to lift damaging Western sanctions that have hit his economy hard and prevented oil companies from doing business in the country.
"We are determined to continue negotiations with our interlocutors in earnest and good faith, based on mutual respect and confidence," Rouhani said of the nuclear talks.
In words that echoed Obama's a day earlier, the Iranian leader said a nuclear deal would be a "historic opportunity" that would send a message of "peace and security."
The five permanent members of the UN Security Council plus Germany are seeking to scale back Tehran's nuclear activities by November 24. Thorny talks have taken place on the sidelines of the General Assembly.
US Secretary of State John Kerry met late Thursday for three-way talks with his Iranian counterpart Mohammad Javad Zarif and EU foreign policy chief Catherine Ashton as they push for a nuclear deal by the deadline.
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A State Department official said the talks would "take stock of the work that has been done this week and discuss the path forward."
There will be further talks between the trio on Friday.
Iran wants UN and Western sanctions lifted, and is pushing for the right to enrich uranium, a process which can produce material for a bomb.
It has long denied it is seeking to develop a nuclear arsenal.
Rouhani met late Thursday with German Foreign Minister Frank-Walter Steinmeier, who said they had "good and intense talks.
"I think we can say that we have never been closer in the past 10 years than we are now, but the truth is the last part of the journey, that is still ahead of us, is probably the most difficult. There are still obstacles to overcome," Steinmeier said.
Negotiators say there are major hurdles to overcome and a July deadline to secure a deal has already been missed.
Western nations agreed to lift some sanctions against Iran last year in exchange for an agreement from Tehran to curb some nuclear activities and to get to work on a comprehensive agreement.
COURTED BY EUROPEAN LEADERS
At the UN for a second time since being elected in 2013, Rouhani has been courted by European leaders seeking greater support from Tehran in the war on IS, responsible for beheading two Americans and one British hostage.
Tehran has been unusually accepting of the US military action against jihadists in Iraq, where Iranian advisors are also tackling IS, but is a strong backer of the Syrian government -- a regime Washington says has no legitimacy.
Underlining the growing importance that the West affords Tehran, British Prime Minister David Cameron held landmark talks with Rouhani on Wednesday, leading Cameron to declare that Iran could be "part of the solution."
They were the first such talks between Britain and Iran since the 1979 Islamic revolution.
Rouhani also met French President Francois Hollande for a second time.