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.
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.
The White House also says Russia has been trying to deflect blame for the chemical attack that killed 89 people.
US intelligence reports say the Syrian government used chemical weapons during air strikes on the rebel-held Syrian town of Khan Sheikhoun that left 89 people dead. The Turkish health ministry on Tuesday confirmed that the nerve agent Sarin had been used.
Syria denies this and Moscow has instead blamed rebel forces, which it says were storing chemical weapons which were hit in the raids.
The UN Security Council is to vote on Wednesday on a draft resolution by the US, UK and France requiring the Syrian government to co-operate with an investigation into the chemical attack.