Iran faces increased US pressure and looming sanctions after Trump's decision to withdraw the United States from a 2015 worldwide deal over Iran's nuclear program.
Iran's President Hassan Rouhani attends a news conference at the Chancellery in Vienna, Austria July 4, 2018.
According to Iranian news agency IRNA, Khamenei considered - during a meeting with Iranian foreign minister Javad Zarif and a number of ambassadors and diplomats - that there is "no benefit of negotiating with America".
According to a Reuters report, the United States is trying to foment unrest in Iran to force the government to abandon its nuclear program and support of terror groups.
Trump announced on May 8 that Washington was walking away from a nuclear agreement, officially known as the Joint Comprehensive Plan of Action (JCPOA) signed between Iran and the P5+1 group of countries in 2015.
Rouhani scoffed at Trump's threat to halt Iranian oil exports and said Iran has a dominant position in the Gulf and the Strait of Hormuz, a major oil shipping waterway.
"The United States has basic and fundamental problem with the (Islamic) establishment", Khamenei was quoted as saying.
Iran's Supreme Leader Ayatollah Ali Khamenei has supported a suggestion by President Hassan Rouhani who hinted earlier this month that Tehran may block regional oil exports if its own sales are stopped following the US' withdrawal from a 2015 nuclear deal with world powers.
Iranian officials have in the past threatened to block the Strait of Hormuz, a major oil shipping route, in retaliation for any hostile USA action.
"The word and even the signature of the Americans can not be relied upon, so negotiations with America are of no avail", Khamenei's official website quoted him as saying.
But Khamenei said talks with the U.S. had proven to be "a blatant mistake" and "useless", claiming Washington would not be satisfied until the current regime was gone.
"The US seeks the return of the situation and their status before the (1979 Islamic) revolution in Iran", said Khamenei.
But it has since eased its stance, saying it may grant sanction waivers to some allies that are particularly reliant on Iranian supplies.