Khamenei says US 'enmities' towards Iran will not end with Trump
He reiterated his position that Iran should bolster itself to "nullify" sanctions imposed by the Trump administration, but should "not delay" in the event they can be lifted.
"You witnessed what Trump's America and Obama's America did to you," he was quoted as saying on his official website.
"Enmities are not limited to Trump's America and will not end just because he has left office," Khamenei added, addressing the family of top Iranian general Qasem Soleimani, who was killed in a January US air strike in neighbouring Iraq.
"Do not trust the enemy, this is my explicit advice."
Tensions between Tehran and Washington soared during Trump's presidency, especially after 2018, when he pulled Washington out of a landmark nuclear deal and reimposed punishing unilateral sanctions.
President-elect Joe Biden, who defeated Trump at the ballot box in November, has signalled a willingness to return to diplomacy with Iran, but Khamenei has on previous occasions cautioned against hopes of an opening with the West.
His remarks come shortly after President Hassan Rouhani said that Iran was "very happy" that Trump was leaving the White House.
Rouhani's government has repeatedly signalled its openness to the incoming US administration and called on Washington to return to the nuclear deal and lift sanctions.
Khamenei underlined that if sanctions "can be lifted, we should not delay it for even an hour."
But he warned: "Do not rely on (others') promises to solve the people's problems (and) do not forget enmities.
"I will support the country's authorities on the condition that they remain true to the nation's goals."
Khamenei's meeting with the slain general's family was his first public engagement since an official close to his office moved to squash rumours about his health last week.