US Secretary of State John Kerry said he and Russian Foreign Minister Sergei Lavrov had agreed to look for ways to revive a Syrian peace plan.
However, he admitted that doing so would be extremely difficult.
Mr Kerry also backed away from earlier comments suggesting he was calling for increased NATO contingency planning on Syria.
He was speaking after talks with Mr Lavrov and NATO colleagues in Brussels.
Mr Kerry said he and Mr Lavrov had discussed ways to revive a peace plan agreed in Geneva last June that called for a transitional government.
He said that while there might be a difference of opinion between Russia and the United States about when and how Syrian President Bashar al-Assad might leave office, "I don't think there's a difference of opinion that his leaving may either be inevitable or necessary to be able to have a solution."
But, he stressed: "I would say to you that it's a very difficult road ... No one should think there is an easy way to move forward on this."
Moscow has for months been calling for implementation of the Geneva Declaration agreed by world powers including Russia and the US, but disagrees with Washington's assertion that it requires Mr Assad to step down.
Mr Lavrov said last week that pressing for Mr Assad's removal would increase the threats posed by militant Islamist groups such as the rebel al-Nusra Front, which formally pledged allegiance this month to al-Qaeda leader Ayman al-Zawahri.
Mr Lavrov told a news conference the Geneva agreement could "not be interpreted in various ways; it has no ambiguity."
"Everyday more people are killed. However I see a growing understanding of the urgency to go from calls for election to real actions. That is why I hope we will see concrete actions on everybody's side," he said.
Mr Kerry said in a statement to a meeting of NATO ministers earlier that the alliance needed "to consider its role in the Syrian crisis, including how practically prepared it was to respond to a potential chemical weapons threat".
NATO Secretary-General Anders Fogh Rasmussen said the alliance was "extremely concerned about the use of ballistic missiles in Syria and the possible use of chemical weapons."
He said the alliance was worried about the risk of the conflict spilling over Syria's borders and said the alliance was willing to defend Turkey.
US President Barack Obama has called the use of chemical weapons a "red line" for the United States that would trigger unspecified US action.