Mr Ahmadinejad's remarks were the first since Mr Obama took office
Iran's president has responded to an overture by the new US president by demanding an apology for past US "crimes" committed against Iran.
The US "stood against the Iranian people in the past 60 years", Mahmoud Ahmadinejad said during an address in the western region of Khermenshah.
"Those who speak of change must apologise to the Iranian people and try to repair their past crimes," he said.
The US president has offered to extend a hand if Iran "unclenched its fist".
President Barack Obama discussed the possibility of a softening of US policy towards Iran in an interview recorded with a Saudi-owned Arabic TV network on Monday.
Mr Ahmadinejad will, as expected, stand for re-election in June, close aide Aliakbar Javanfekr told Reuters news agency on Wednesday.
America's crimes against Iran, the Iranian leader said in his televised speech, included support for the Iranian coup of 1953 and backing for Saddam Hussein in the Iran-Iraq war of the 1980s.
The Iranian president welcomed the possibility of US change, but said it should be "fundamental and effective" rather than just a change of tactics.
The remarks are the first Iranian comment on the US since Mr Obama took office eight days ago.
The BBC's Jon Leyne in Tehran describes it as one of Mr Ahmadinejad's strongest tirades against the US.
Our correspondent says we may see twists and turns out of Iran as its leaders work out whether Mr Obama is offering real change and what they may offer in return.
While he was playing to the crowd, adds our correspondent, he could also be staking out his position ahead of Iran's presidential election in June.
Mr Ahmadinejad congratulated Mr Obama after his election in November but the message was criticised in Iran and received a cool response from Mr Obama.
'Hell' for Bush
Mr Ahmadinejad also attacked US support for Israel and its wars in Afghanistan and Iraq.
He called on Mr Obama to withdraw US troops from their bases around the world and for America to "stop interfering in other people's affairs".
Referring to Mr Obama's predecessor, George W Bush, he said he trusted that he had "gone to hell".
Relations between Washington and Tehran reached new lows in recent years over attempts by the US and its allies in the United Nations to curtail Iran's nuclear programme over fears it is trying to build nuclear weapons.
Tehran says its programme is to develop civilian nuclear power only.
The new US ambassador to the UN, Susan Rice, said on Monday that she was looking forward to "vigorous diplomacy that includes direct diplomacy with Iran".
The US broke off diplomatic ties with Iran in 1979, after students stormed the US embassy in Tehran after the Islamist revolution overthrew the US-backed Shah.