"I find it strange that they (Americans) talk about Middle East stability and peace and the other beautiful principles and call for two countries to move away from each other," al-Assad said.
Ahmadinejad was more direct, calling for the US to pack up and leave the Middle East.
"(The Americans) want to dominate the region but they feel Iran and Syria are preventing that," he said.
"We tell them that instead of interfering in the region's affairs, to pack their things and leave."
According to some reports the Iranian president will meet Sheikh Hassan Nasrallah, the secretary general of the Lebanese group Hezbollah, while in Damascus.
He met Khaled Meshaal, the political chief of Hamas, on Wednesday.
Ahmadinejad's trip comes amid rising US tension with Tehran over the country's nuclear programme.
Testifying in the senate, Hillary Clinton was blunt about Washington's bid to drive a wedge between Damascus and Tehran - the target of a US-led drive for UN sanctions designed to halt Iran's contested nuclear programme.
Clinton said Washington is asking Syria to "generally to begin to move away from the relationship with Iran, which is so deeply troubling to the region as well as to the United States."
Al-Assad, instead, signalled his strong support for Iran, saying America's stance towards the Islamic Republic "is a new situation of colonialism in the region."
"We must have understood Clinton wrong because of bad translation or our limited understanding, so we signed the agreement to cancel the visas," he said.
The United States accuses Syria and Iran of supporting armed groups in the region, including Hezbollah as well as Hamas, the Palestinian political movement that controls Gaza.
Both Iran and Syria deny that they provide anything other than moral support to Hezbollah.
The US and the US-backed Iraqi government frequently say Damascus is not doing enough to stop anti-US fighters, including those from al-Qaeda, from crossing the border into Iraq.
Still, al-Assad could be open to a breakthrough with the Americans. He is hoping for American mediation in direct peace talks with Israel to achieve his top goal of winning the return of the Golan Heights, occupied by Israel in the 1967 Mideast War.
|Iran has already been slapped with three sets of UN sanctions over its uranium enrichment
The administration of Barack Obama, the US president, has pursued a year-long campaign to engage Syria, a former US foe, and energise its thwarted push for a broad Arab-Israeli peace, particularly between Israel and the Palestinians.
Obama last week announced that Robert Ford will be the first US ambassador to Damascussince Washington recalled its envoy after Lebanon's former prime minister Rafiq al-Hariri was killed in February 2005 in a bombing blamed on Syria.
Analysts say engagement is likely to produce modest benefits such as better intelligence co-operation and an improved climate for peace, rather than peel Syria away from a strategic ally like Iran or achieve a peace breakthrough.