Iran President Ahmadinejad said ties between his country and Syria remain "deep" and attacked U.S. involvement in the Middle East.
"The Americans want to dominate the region but they feel Iran and Syria are preventing this," he said. "We tell them that instead of interfering in the region's affairs, to pack their things and leave."
In recent months the Obama administration has launched new efforts to re-engage with the Syrian regime including the re-establishment of an ambassador in Damascus, the first since 2005.
As the pressure mounts to impose tougher sanctions on Iran over its secretive nuclear program, many in Washington hope warmer relations with Syria will drive a wedge between two members of what President George W. Bush once famously dubbed the Axis of Evil.
Thursday's summit in Damascus appears designed to present a united front against such efforts.
As usual Israel was also the target of Ahmadinejad's fiery rhetoric. In recent weeks the region has been abuzz with talk of war, with both Syria and the Lebanese group Hezbollah exchanging threats with Israel.
"If the Zionist regime wants to repeat its past mistakes, this will constitute its demise and annihilation," the Iran president said. "With Allah's help the new Middle East will be a Middle East without Zionists and Imperialists."
Syrian officials have been issuing increasingly bellicose statements against Israel and has promised to support Hezbollah in the event of conflict, a commitment underscored Thursday by Syria President Assad.
"We believe we are facing an entity that is capable of aggression at any point, and we are preparing ourselves for any Israeli aggression, be it on a small or large scale," he said.
During his stay in Syria, Ahmadinejad is also expected to hold meetings with leading figures from Hezbollah and the Palestinian Islamic group Hamas. Both organizations are thought to receive arms and funding from Tehran.