Hugo Chavez made the observation on Tuesday in front of a rally of cheering supporters. It was the latest salvo in a war of words between Washington and Caracas.
He said the United States was making it impossible for there to be peace in the world, a comment he said was a response to recent criticism from George Bush, the US president.
"We are very worried because your imperialist and war-like government is dangerously eroding the possibility of peace and life in the world," Chavez said. Chavez is a critic of the war on Iraq.
Bush had said on Monday he was concerned about what he called the erosion of democracy in Venezuela and Bolivia.
The US administration says that Chavez is trying to destabilise Latin America and the Venezuelan leader accuses the White House of planning to overthrow him to snatch the country's vast oil reserves.
Chavez told the rally: "The United States is now a country against its own people and against the people of the world. It is anti-democratic.
"They called the 20th century the American Century. Fine. The 21st century will be called the century that saw the end of the North American empire."
Evo Morales, the president of Bolivia, nationalised the country's energy industry on May 1, upsetting international investors.
"They called the 20th century the American Century. Fine. The 21st century will be called the century that saw the end of the North American empire"
He and Chavez are close allies and, with Fidel Castro, the president of Cuba, have formed an alliance that aims to stifle what they say is US hegemony in the region.
The US announced this month it would no longer sell arms to Venezuela, insisting the country had failed to co-operate in efforts to fight terrorism.
Chavez denies that and has accused the US of being behind a botched 2002 coup that briefly toppled his government. US officials dismiss his accusations.