"They stealthily and cowardly assassinated Gen. Soleimani in a terrorist fashion. This resulted in a disgrace for America," Khamenei said as he led the prayers in Tehran's Imam Khomeini Grand Mosque, where huge crowds of worshipers had already gathered from early Friday morning.
Regarding the January 8 Iranian missile attack on two military bases in Iraq that houses US troops which was in retaliation of Soleimani's death, Khamenei said that Tehran's response "dealt a blow to the American prestige", reports Press TV.
The attack was a "military blow, but more important it was a blow to the American grandeur", he added.
Khamenei also lashed out at British, German and French leaders who admitted this week to have launched a process that could lead to European sanctions being reimposed on Iran.
"You are too small to bring the Iranian nation to its knees," he said.
Meanwhile, massive anti-US protest rallies were expected to be held after the prayers.
The last time Khamenei led Friday prayers in Tehran was in 2012 on the 33rd anniversary of the country's Islamic Revolution.
Friday's prayer service also came in the wake of widespread protests over the January 8 downing of the Kiev-bound Ukraine International Airlines Boeing 737-800 by an Iranian missile shortly after it took off from Tehran, killing all 176 people on board.
The protests erupted across Iran after the Islamic Revolutionary Guards Corps on January 12 admitted that the plane had been mistaken for a "cruise missile" during heightened tensions with the US.
( With inputs from IANS )