Huge crowds of Iranians, mostly school and university students, demonstrated in more than 770 cities as part of the "National Day against Global Arrogance," Tasnim news agency reported.
In Tehran, demonstrators in front of the former U.S. diplomatic compound said in their statement they considered the United States the "Great Satan and the nation's No. 1 enemy."
On Nov. 4, 1979, less than a year after the Islamic Revolution toppled a U.S.-backed monarchy, Iranian university students seized the U.S. Embassy in Tehran. The Islamist students held 52 embassy staff members hostage for 444 days, severing diplomatic relations and provoking decades of mutual hostility.
Observers told Voice of America Monday's rally was the biggest in years at the annual event on the former U.S. compound. Hardline conservatives called for a major showing to protest President Hassan Rouhani's historic outreach to Washington.
A 15-minute telephone conversation after the U.N. General Assembly between U.S. President Obama and Rouhani in September was the first direct contact between the two countries' top leadership in more than three decades.
Iran's supreme leader Ayatollah Ali Khamenei has voiced support for President Rouhani's overtures to the West, but says some of the president's moves were "not appropriate."