"No matter how much they confront us, accuse us and put barriers on our way, it might only slow our movement, but they cannot stop us," Ayatollah Ahmad Janati said in a Friday prayer sermon.
"In this nuclear issue, we are the winner, not America. They must know this. Today, there is no grounds for the US bullying in the world, especially in Iran," he added, drawing the usual chants of "Death to America!".
Janati heads Iran's powerful Guardians Council, an unelected constitutional watchdog that screens all laws and chooses who can and cannot stand for public office.
Iran has defied the international community by resuming work on making power reactor fuel that could also be used to make nuclear weapons but insists that it wants to continue talks on guaranteeing its atomic program is peaceful.
The country restarted uranium conversion work in response to demands from Britain, France and Germany that it abandon the nuclear fuel cycle -- the focus of fears Iran could acquire the bomb but technically permitted by the nuclear Non-Proliferation Treaty (NPT).
The United States, which accuses Iran of seeking nuclear weapons, is lobbying at the International Atomic Energy Agency (IAEA) for Iran to be referred to the UN Security Council for possible sanctions.