Speaking in person at the UN's New York headquarters on Wednesday, Pezeshkian described Iran as a "victim of terrorism" and rejected any acceptance of limits on its nuclear program or capitulation to military and economic pressure.
"Yesterday, the United States' president described us as terrorists," he said, according to a live translation. "We have been the victims of terrorism."
"We will never bow our head or bend at the knee," he added. "Iran must be understood by Mr Trump and those who seek to bully us that we are ready for dialogue and diplomacy and negotiations without accepting the language of force."
Responding directly to Trump's threat, Pezeshkian said: "He must know that the resistance of the Iranian people will only increase in the face of sanctions, increased pressure, increased bullying."
During the address, he held up a photo of the late Supreme Leader, Ayatollah Ali Khamenei, who was killed in a strike on his residence when the US and Israel launched a joint attack in late February. The speech also accused the US and Israel of terrorism for the thousands of civilian deaths in their military campaigns in the Middle East.
Pezeshkian insisted any deal would have to include an end to the US blockade of Iranian ships and ports. "It cannot be the case that everyone benefits from the Strait of Hormuz while we are denied access," he said.
The Strait of Hormuz, through which a fifth of global oil and gas shipments usually pass, has effectively been closed since the start of the war due to Iranian missile and drone attacks on commercial vessels and the US blockade. A preliminary agreement to end the war and reopen the strait was reached in June but collapsed within weeks when Iranian attacks on shipping resumed.
The defiant speech came as indirect talks resumed on the sidelines of the assembly. Iranian Foreign Minister Abbas Araghchi and US envoy Steve Witkoff held indirect discussions brokered by Qatari mediators — the first since June. Witkoff said he hoped the talks would "prove constructive and promising," but Iran's foreign ministry spokesman Esmail Baqai dismissed them as "not anything new," saying Araghchi had maintained Iran's conditions including the end of the blockade and the release of frozen Iranian assets.
Ali Vaez, an Iran analyst at the International Crisis Group, said the speech was a "reminder that the US military and economic pressure on Iran can create leverage but don't necessarily produce capitulation." He added: "As long as there's a leadership in Tehran that believes its survival to be at stake, it'll opt for endurance rather than surrender. But what happens in the corridors of the UN this week, in direct and indirect talks, matters more than what either side says at the podium."
Pezeshkian, who was afforded the protection of the US Secret Service as is protocol for visiting leaders, was believed to be the first world leader to address the UN assembly while at war with the host country.