State TV quoted Mr Khamenei addressing thousands of Iranians: "I ban holding any talks with America".
Trump's determination to push ahead with sanctions on Tehran which also target European companies doing business with Iran has opened another battle front.
Several European companies have suspended plans to invest in Iran in light of the USA sanctions, including oil major Total as well as carmakers PSA, Renault and Daimler.
Khamenei said Monday that the monetary crisis resulted from "management problems unrelated to sanctions" and blamed the administration of Iranian President Hassan Rouhani, the news service added.
The Leader also said, "There will be no war, because, as it was in the past, we will never initiate a war and nor will the USA start a war, because it will be totally harmful to them".
Ayatollah Ali Khamenei's statement was an apparent attempt to deflect public anger over the plunging worth of the rial - the currency has lost about half of its value since April - and wider economic woes due to tough new USA sanctions on Tehran.
The rial has lost about half of its value since April in anticipation of the renewed USA sanctions, driven mainly by heavy demand for dollars among ordinary Iranians trying to protect their savings.
"America's withdrawal from the nuclear deal is a clear proof America can not be trusted", Mr Khamenei told a gathering of thousands of Iranians. "I do not call it betrayal but a huge mistake in management", Khamenei said.
Thousands of Iranians have protested in recent weeks against sharp rises in the prices of some food items, a lack of jobs and state corruption.
As Middle East Eye reported last month, the govenrment's attempt to unify the dollar's official and black market exchange rates completely backfired. The protests over the cost of living have often turned into anti-government rallies.
Washington reimposed the sanctions last week after pulling out of a 2015 worldwide deal aimed at curbing Iran's nuclear program in return for an easing of economic sanctions. He says Iran must change the way it operates, including its activities in Syria and Yemen.
Washington this week reimposed sanctions on Iran's purchase of USA dollars, its trade in gold and precious metals and its dealings with metals, coal and industrial-related software.
"Not that sanctions don't have an impact, but the main factor is how we handle them".