The West and allies fear that Iran's uranium enrichment labs could eventually produce weapons-grade material. The Islamic Republic claims it only seeks nuclear fuel for energy reactors and medical applications.
The U.S. and Iran broke ties after the storming of the American Embassy in Tehran in the wake of the 1979 Islamic Revolution. Iranian militants held 52 American hostages for 444 days.
"I am not a diplomat. I am a revolutionary and I express my words honestly," Khamenei was quoted as saying.
He noted that some factions inside Iran seek the direct U.S. talks due to their "naivety." He did not elaborate, but called for the need to challenge U.S. efforts to return "domination" over Iran — a reference to the pro-Western shah that was toppled by the Islamic Revolution.
"Talk is meaningful if it is based on goodwill, equal standing and when both sides do not want to apply tricks," said Khamenei. "Talk as a tactic, a gesture of superpower, is only a deceptive move."
Khamenei, however, has shown some flexibility in the past over contacts with Washington. Iran and the U.S. have taken part in talks regarding Iraq and Afghanistan.