It was unclear whether the envoys would meet Bashar al-Assad, Syria's president.
Rula Amin, Al Jazeera's correspondent reporting from Damascus, described the visit as "very significant".
"Jeffery Feltman said he is here to address a long list of concerns for the US with the Syrians," she said.
"Before this administration it was a confrontational policy ... and now this administration seems to think that Syria could be key to resolving many of the hot issues on President Obama's plate."
Amin said that this included the situations in Iran, Iraq, Palestine, Israel and Lebanon.
"Syria has been Iran's strongest partner in the region, and that is how Iran extends its influence in the Middle East," she said.
"They think that if they disengage Syria from Iran, that would weaken Iran and make it easier for the US to negotiate with Iran and to impose its terms."
The US withdrew its ambassador from Damascus after the assassination of Rafiq al-Hariri, the former Lebanese prime minister, in 2005, and stepped up sanctions against Syria.
Damascus maintained a military presence in Lebanon for 29 years until al-Hariri's death, when Lebanese and international pressure forced their removal.
Syria has never admitted a role in al-Hariri's death but many suspect its involvement.