The White House said Tehran was in no position to make such comments after crushing its own uprising last year.
"Do not back down until the implementation of a popular regime based on religion," said Khamenei, Iran's commander-in-chief, who switched from Persian to Arabic during his Friday sermon directed at Egyptians.
"The clergy should play a role. For example, when people come out of mosques and chant slogans, they should support. Inshallah (God willing) part of the Egyptian army will join the people. The main enemy of the Egyptian army is the Zionist regime and not the people," he said.
He called the Arab revolts "a real earthquake" that if successful would lead to "failure of American policies" in the Middle East.
Washington reacted by pointing to mass protests in Iran following the June 2009 re-election of President Mahmoud Ahmadinejad in an election opponents said was rigged.
"It is remarkable that Iran would make a statement given their actions when it came to their people exercising the same rights that people are exercising now in Cairo," White House spokesman Robert Gibbs said.
Khamenei on Friday called Mubarak the "servant" of Israel and the United States.
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