The theocratic head of Iran was speaking to students ahead of the anniversary of the Iran Hostage Crisis of 1979.
Khamenei said the comments Clinton and Trump had made in the presidential debates "are sufficient for the annihilation of the reputation of the United States."
He reiterated his remarks on Twitter and cast the presidential candidates' debate performances as a confirmation of what Iran had already said about the United States.
"In US presidential #debates two candidates revealed facts & calamities from US parts of which we had told before but some didn't believe it," Khamenei said.
The hard-line ruler -- whose nation the United States has designated a state-sponsor of terror and called out for "severe restrictions on civil liberties" as well as a "disregard for the physical integrity of persons" -- also said the "US system is far away from values of humanity. 'Death to America' means death to a system which has nothing to do with humanitarian values."
On Twitter, Khamenei said Clinton and Trump underscored America's "collapse of humanitarian values" and described the US as a racist country where 1% of the population has access to 90% of the wealth.
According to Iranian state media, Khamenei also dismissed negotiations with the United States, saying such talks "will not resolve our problems." He added, "We should resolve the problems ourselves and with reliance on our capabilities and the young forces inside the country."
Despite allowing Iran to sign an agreement with the United States, the UK, France, China, Russia and Germany limiting Tehran's nuclear program, Khamenei has continued to criticize negotiations with the United States.
Clinton has indicated her support of the deal, and Trump has made his opposition to the Iran deal a regular feature of his campaign.
The Iran Hostage Crisis began 37 years ago when Iranian revolutionaries seized the US Embassy and held 52 US citizens captive for 444 days.