"Realities in the region show that the arrogant front, headed by U.S. and its allies, will be the principal loser in the region," the broadcast quoted Khamenei as saying in meeting Syrian President Bashar Assad.
Assad left Iran on Sunday after a two-day visit to discuss Iraq and other regional issues with senior Iranian officials, including Khamenei and President Mahmoud Ahmadinejad.
During his visit, Assad accused the U.S. and Israel of trying to harm the regional positions of Iran and Syria by raising questions about their roles in Iraq, Lebanon, and Palestine.
"Through effort and coordination, we have to enlighten public opinion about the ominous aims of the U.S. and Zionists," said Assad, the official Islamic Republic News Agency reported.
Ahmadinejad expressed similar concerns when he accused the U.S. and Israel of targeting Islamic countries under the pretense of achieving peace.
"They imply that they are pursuing peace and security in the region, however they want to improve their and the Zionists' position in the region and hit Islamic countries," IRNA quoted Ahmadinejad as saying.
The U.S. has accused Syria of not doing enough to prevent militants from crossing its border into Iraq and has blamed Iran for supporting Shiite militias in attacks that have killed American troops. U.S. officials also accuse Iran and Syria of interfering in Lebanon and the Palestinian-Israeli conflict through supporting Hezbollah and Hamas, both of which the U.S. considers terrorist groups.
Iran and Syria have long been close allies. During the 1980-1988 Iran-Iraq war, Syria was the only Arab country to support Iran.
During the past 10 years, Iranian companies have invested more than $700 million in Syria, in sectors such as power generation, automobiles, cement and agriculture.