US Secretary of State Rex Tillerson is to urge Russia to stop supporting Syrian President Bashar al-Assad, during talks in Moscow.
The visit comes amid rising tensions over last week’s chemical weapons attack in Syria and US air strikes on a Syrian airbase launched in response.
Russia has condemned the US strikes and stood by Syria, its long-time ally.
President Trump has made clear the US had no further plans there and was “not going into” that country’s civil war.
On Tuesday his defence secretary said the priority remained the defeat of the Islamic State jihadist group. “Our military policy in Syria has not changed,” Jim Mattis said.
Last week’s air strike has led to confusion over US policy in Syria, with some officials suggesting a more aggressive stance against President Assad.
Mr Tillerson will hold talks with Foreign Minister Sergei Lavrov after warning that Russia risks becoming irrelevant in the Middle East because of its support for Mr Assad.
He also insisted Syria’s president can play no part in the country’s future.
However, the BBC’s Steve Rosenberg in Moscow says President Assad is Russia’s key military ally in the Middle East and Mr Tillerson may need to rethink his belief that he can weaken Moscow’s support for him.