Ayman al-Zawahiri, the No 2 man in Al Qaeda, slammed US policies in a videotape aired on Sunday on Arabic-language TV station Al Jazeera.
With respect to the US' statements that it wants to extend democracy around the world, he said, "Your new crusade will end, God willing, with the same defeat as its predecessors, but only after you have suffered tens of thousands of dead and the destruction of your economy."
He said the message was to mark the third anniversary of the internment of Muslims at the US military base of Guantanamo Bay, Cuba.
Reports have emerged showing how US troops tortured the prisoners there.
"Guantanamo exposes the reality of the reform and the democracy that America is trying to spread in the region," he said.
Zawahiri added that if people believe the "so-called elected governments will protect you, you are wrong".
He said the "security of the West" is based on how it deals with Muslims "and ending all foreign occupation".