Hugo Chavez made the remarks on Tuesday as the UN Security Council failed to agree on how to respond to Iran's nuclear programme and the US government said Tehran could blackmail the world if it were to develop an atomic bomb.
"The US imperialists invaded Iraq looking for oil and now they are threatening Iran for oil, not because the Iranians are developing some kind of nuclear bomb, that is a lie, there is no evidence of that," Chavez said at a ceremony.
Riling the US
The Venezuelan leader, whose close ties to Cuba and Iran have annoyed Washington, has supported the Iranian government while Western powers try to halt its nuclear energy programme because they say Tehran is secretly trying to make nuclear weapons.
"The US empire is defeated in Iraq ... God help them if they try to attack Iran," Chavez said to applause at a public event later. "We ask for and want peace, but over there they would taste double the dust of defeat.
"This is the century of the grave for US imperialism"
Hugo Chavez, the president of Venezuela
"I really believe the US empire is waiting for its grave. This is the century of the grave for US imperialism."
Venezuela and fellow Opec member Iran have strengthened their ties with commerce and energy accords as Chavez seeks to break his country's economic reliance on the United States.
Chavez has become one of Iran's loyal defenders in its nuclear dispute.
Venezuela was one of the few countries to vote against an International Atomic Energy Agency resolution to send Iran to the UN Security Council over its atomic work.
Tehran dismisses US and European claims and says its programme is for peaceful civilian uses.