Ayatollah Ali Khamenei also told worshippers that widening unrest in the Arab world is a sign of "Islamic awareness" in the region.
Iran has portrayed the unrest in Egypt, which erupted Jan. 25, as a replay of the 1979 Iranian Revolution that toppled the pro-U.S. Shah and brought Islamic militants to power.
In his speech, Khamenei accused Mubarak of turning Egypt, a close U.S. ally, of doing America's bidding, particularly in the Israeli-Palestinian conflict. Egypt was the first Arab country to sign a peace agreement with Israel and Mubarak has been a key mediator between Israel and the Palestinians.
"America's control over Egypt's leaders has ... turned Egypt into the biggest enemy ofr Palestine and turned it into the greatest refuge for Zionists," Khamenei said.
"This explosion we see among the people of Egypt is the appropriate response to this great betrayal that the traitor dictator committed against his people," Khamenei said, without mentioning Mubarak by name.
Despite Iran's attempts to compare Egypt's uprising to the 1979 Islamic revolution in Iran, there are many differences. Egypt's Muslim Brotherhood is perhaps most organized of the opposition factions, but the protests have been driven by a loose alliance of diverse groups, including young, secular Egyptians.
The Brotherhood, which is officially banned, calls for rule by Islamic law in Egypt. But it has also cast itself in an uneasy partnership with pro-democracy advocate Mohamed ElBaradei and other opposition groups.