The annual speech on the first day of the Persian year serves as a sort of Iranian equivalent to the US State of the Union address, and Khamenei used it to provide more details about his calls for a self-sufficient "resistance economy" that has been his main theme in recent months.
"The importing of products where an Iranian equivalent exists should be considered religiously and legally haram (forbidden)," he told a huge crowd in the holy city of Mashhad.
He took aim at Iran's rampant black market in smuggled goods, which he said was worth at least $15 billion annually.
"Some speak of $20-25 billion," he said.
"We want greatness for our country, social well-being and security at the national level. Without a strong economy we cannot achieve all that."
Signup to our newsletter and follow us on Facebook and Twitter!
Khamenei said President Hassan Rouhani's government deserved credit for its economic achievements over the past year, but his praise was guarded.
"Certain official figures do not convince the public. We must redouble our efforts. The statistics show that inflation has fallen but at the same time unemployment has risen," he said.
Rouhani, who is expected to stand for a second term in May, has touted his successes in reducing inflation from 40 percent to less than 10 percent, and ending global sanctions through a nuclear deal with world powers.
But while that has led to a boost in oil sales and growth of more than six percent, much of the economy remains stagnant.
Analysts say deep structural reforms are needed, particularly in the banking sector.
Global banks still refuse to finance large-scale foreign investments in Iran, fearing its murky business environment and uncertainty over continuing US sanctions.