"Last night, a slap in the face was delivered," Ayatollah Ali Khamenei said in a speech broadcast live on state television.
His remarks came after he had vowed "severe revenge" for a US drone strike that killed Iranian military commander Qasem Soleimani near Baghdad international airport last week.
Shortly after midnight, Iran fired a series of missiles at bases in Iraq housing US troops, officials in Washington and Tehran said.
"One important issue is what is our duty now?" following Soleimani's assassination, said the supreme leader.
"An important incident has happened. The question of revenge is another issue," said Khamenei.
"Military actions in this form are not sufficient for that issue," he said, referring to the assassination.
"What is important is that America's corrupt presence must come to an end in this region."
Soleimani was one of Iran's most popular public figures. He was laid to rest in his hometown early on Wednesday morning after massive funeral processions in several major cities of Iran.
Iran missile attacks target US forces in Iraq
Iran's President Hassan Rouhani told US that Washington might have "cut off the arm" of General Qassem Soleimani but America's "leg" in the region would be cut off in response, Iran's Fars reported.
President Rouhani made his comments after Iran launched missile strikes on US targets in Iraq, an action that Tehran said was in retaliation to a US drone strike that killed Soleimani last week.
Iran's Foreign Minister Mohammad Javad Zarif said that US assessment on Tehran’s missile attacks should not be based on "illusions".
Zarif also said that Tehran's missile attacks on US targets in Iraq were “legitimate self-defence.”
Iran's response to US retaliation to Tehran's missile attacks on American targets in Iraq will be proportional, Iranian Defence Minister Amir Hatami told state television.
"We used short-range missiles ... I hope this will be a memorable lesson for America," Hatami said.
"Iran's response (to any US retaliation) will be proportional to what America will do," he said, adding that US President Donald Trump "has turned the (US) Administration into a terrorist government."
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