US secretary of state Rex Tillerson has said Russia must abide by a 2015 deal aimed at ending fighting between Ukrainian forces and Russia-backed separatists.
The former Exxon Mobil chief executive spoke after meeting Russian foreign minister Sergey Lavrov for the first time in the highest level face-to-face contact between representatives from the two countries since Donald Trump took office on January 20.
Russia annexed the Crimean Peninsula from Ukraine in 2014, and Russian-speaking separatists began protests that escalated into a war, with thousands killed.
A deal two years ago known as the Minsk agreement was intended to end the conflict, but skirmishes have continued.
"As we search for new common ground, we expect Russia to honour its commitments to the Minsk agreement and work to de-escalate the violence in the Ukraine," Mr Tillerson said after talks with Mr Lavrov.
US General Joe Dunford, chairman of the Joint Chiefs of Staff, was set to meet with his Russian counterpart, General Valery Gerasimov, in the former Soviet republic of Azerbaijan.
It was to be the first meeting between the two countries' senior members of the military since Mr Trump was sworn in.
Mr Tillerson has taken a low-key and reserved approach in his first two weeks on the job and declined the opportunity to speak with reporters travelling with him aboard his plane to Germany.
He did not respond to reporters' questions at his first three meetings in Bonn and, until Thursday, had yet to comment publicly on developments with Russia, its alleged meddling in the 2016 US presidential election or its actions in Syria and Ukraine.
"As I made clear in my senate confirmation hearing, the United States will consider working with Russia where we can find areas of practical co-operation that will benefit the American people," Mr Tillerson said following the Lavrov meeting.
"Where we do not see eye to eye, the United States will stand up for the interests and values of America and her allies."
The meeting, on the sidelines of a larger foreign ministers conference in Germany, came amid turmoil inside the Trump administration over Russia and the ousting of national security adviser Michael Flynn over misleading White House officials on his contacts with Moscow.
Asked whether the chaos in Washington was a concern to Russia, Mr Lavrov replied: "You should know we do not interfere in the domestic matters of other countries."
In his opening remarks, Mr Lavrov said he and Mr Tillerson had "plenty of issues to discuss" and that they would "discuss and establish the parameters of our future work".
Mr Trump chose Mr Tillerson for the job in part because of his business experience and relationship with Russia while he was at Exxon.
His meeting with Mr Lavrov was seen as a first test of whether that business acumen - which led to great profits for the oil company and Russian President Vladimir Putin bestowing a friendship award upon him - can translate into success in a high-stakes diplomatic arena.
At his confirmation hearing last month, Mr Tillerson voiced conventional concerns about Russia's behaviour and said they should be addressed by projecting a forceful and united front.
Like others in the administration, he has not been specific about how to repair damaged ties or whether doing so might involve lifting US sanctions imposed on Russia after its annexation of the Crimea region.