Rex Tillerson is in Germany for a meeting with G20 leaders on his first foreign trip as US secretary of state.
Mr Tillerson is expected to confirm that the US remains committed to Nato, at the gathering of ministers in Bonn.
He will also meet Russian Foreign Minister Sergei Lavrov at a time when US relations with Moscow are under the spotlight.
Officials said the secretary of state main intention was to listen to his G20 counterparts.
While in Germany, Mr Tillerson will participate in a series of sessions on global issues ranging from conflict prevention to developing cooperation with Africa.
However it is his meeting on Thursday with Mr Lavrov that will be watched most closely.
Mr Tillerson is expected to seek “pragmatic and constructive cooperation in areas where our interests overlap,” a US official told Reuters news agency.
Counterterrorism is one area that the US secretary of state is hoping to “develop some possible avenues for cooperation,” the official said.
Mr Lavrov is likely to use his time with Mr Tillerson to explore the significance of US President Donald Trump’s repeated calls for improved relations with Russia.
But senior state department officials said that Mr Tillerson would not soften Washington’s position on Russia’s interventions in Ukraine, a crisis which remains unresolved.
They added that he would use the talks to urge the Kremlin to abide by its commitments in the Minsk peace agreement.
Mr Tillerson will also meet the UK Foreign Secretary Boris Johnson, with US officials saying he would support a pragmatic Brexit that resulted in a strong Britain, and a strong EU.
The G20 is made up of developed economies and emerging nations including Russia, China, India, Indonesia, Mexico, South Africa and Brazil.
The first task for ministers at the gathering in Germany will be to get Mr Tillerson to spell out exactly what Mr Trump’s “America First” means in practice.