Rex Tillerson’s visit comes amid tensions over last week’s suspected chemical attack in Syria and American strikes on a Syrian base.
Russia has condemned the US strikes and stands by Syrian President Bashar al-Assad, its long-time ally.
President Donald Trump has said the US has no further plans there and is “not going into” that country’s civil war.
On April 11, President Trump’s defense secretary made clear the priority remained the defeat of ISIS.
Jim Matiss said: “Our military policy in Syria has not changed.”
Last week’s air strike has led to confusion over US policy in Syria, with some officials suggesting a more aggressive stance against President Bashar al-Assad.
As they were preparing to meet today, Sergei Lavrov told Rex Tillerson that Russia had “a lot of questions regarding very ambiguous and contradictory ideas (…) coming from Washington”.
Rex Tillerson said he looked forward to a “candid” exchange so that the two countries could better define and narrow their differences.
He has warned that Russia risks becoming irrelevant in the Middle East because of its support for Bashar al-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.
On April 11, the Turkish health ministry confirmed that the nerve agent Sarin had been used.
Syria denies this and Russia has instead blamed rebel forces, which it says were storing chemical weapons which were hit in the raids.
On April 12, the UN Security Council is to vote on a draft resolution by the US, UK and France requiring the Syrian government to co-operate with an investigation into the chemical attack.
President Vladimir Putin has also called for an independent UN investigation.
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