Mr Ahmadinejad told some 3,000 students in Tehran that Israel’s establishment had been a move by the West against the Islamic world.
He was addressing a conference entitled The World without Zionism and his comments were reported by the Iranian state news agency Irna.
“As the Imam said, Israel must be wiped off the map,” he said, referring to Iran’s late revolutionary leader, Ayatollah Ruhollah Khomeini.
In 2001, former Iranian president Hashemi Rafsanjani speculated that a Muslim state that developed a nuclear weapon might use it to destroy Israel.
His comments were part of a critique of what hew called American imperialism in the region.
Such calls are regular slogans at anti-Israeli or anti-US rallies in Iran.
Mr Ahmadinejad warned leaders of Muslim nations who recognised the state of Israel that they faced “the wrath of their own people”.
Mr Ahmadinejad came to power earlier this year, replacing Mohammad Khatami who had sought better relations with the West.
The European Union and Russia have joined condemnation of the Iranian president’s public call for Israel to be “wiped off the map”.
Mahmoud Ahmadinejad’s remark has already been condemned by individual EU states and Canada who all summoned Iranian diplomats for an explanation.
A top Israeli minister called for Iran to be expelled from the United Nations.
The White House said the comment showed the US was right to be concerned about Iran’s nuclear programme.