Tension has steadily ratcheted higher since 2018, when the US withdrew from Tehran's nuclear pact with world powers and reimposed sanctions that have hammered the economy.
The stand-off erupted into tit-for-tat military strikes this month, when Washington killed top commander Qassem Soleimani in a drone strike on January 3 and Iran launched missile strikes at US targets in Iraq on January 8.
In the aftermath, a Ukrainian airliner was shot down by mistake. But it took days for the Guards to admit it and protesters directed their rage at the elite force and the clerical system it was set up to defend.
"Our enemies were happy that they found an excuse to undermine the Guards, the armed forces and our system," Khamenei said in his sermon, heaping praise on the Guards for protecting Iran and renewing a call for US troops to leave the region.
Khamenei said Soleimani's work of projecting Iran's military influence abroad would continue and said the Quds Force he commanded "protects oppressed nations across the region".
He said Quds Force soldiers were "fighters without borders".
The US Department of State's special representative to Iran, Brian Hook, said in Washington that Iranian threats risked further isolating the country. But Russia lent Iran support over the airline disaster, saying it had been shot down when Tehran was spooked by reports of advanced US stealth fighters in the area.
"I'd like to underline the edginess that always accompanies such situations," Foreign Minister Sergei Lavrov said.
KHAMENEI SLAMS 'AMERICAN' CLOWNS'
Protests, led by students, erupted in Tehran and other cities for four days over the shooting down of Ukraine International Airlines flight 752, in which all 176 on board were killed, mostly Iranians or dual nationals.
As the unrest picked up, US President Donald Trump sent tweets in Farsi and English supporting the protesters, who were chanting "Death to Khamenei" and slogans against the Guards.
"These American clowns who lie and say they are with the Iranian people should see who the Iranian people are," Khamenei said in his sermon.
"The plane crash was a bitter tragedy that burned through our heart," he added. "But some tried to use it as an excuse to overshadow the martyrdom of our great commander Soleimani." Stopping short of a direct apology for the plane disaster, he urged Iranians to unite and show solidarity by turning out in numbers for the February parliamentary election.
US President Donald Trump addressed Khamenei's words on Twitter.
"The so-called 'Supreme Leader' of Iran, who has not been so Supreme lately, had some nasty things to say about the United States and Europe," Trump, who is in Florida for a fundraiser, tweeted Friday evening. "Their economy is crashing, and their people are suffering. He should be very careful with his words!"
TRUMP CONTRADICTED
Despite President Trump's earlier statements that "no Americans were harmed" in the January 8 attacks on two Iraqi bases, a spokesman for United States Central Command has claimed otherwise.
"While no US servicemembers were killed in the January 8 Iranian attack on Al Asad air base, several were treated for concussion symptoms from the blast and are still being assessed," Captain Bill Urban said. Urban said the injured troops were taken to American military sites in Germany and Kuwait to undergo screening, and that "when deemed fit for duty, the servicemembers are expected to return to Iraq".
