In a news conference, Clinton said she told Russian President Vladimir Putin and Foreign Minister Sergei Lavrov the United States was adamant in its position on the civil war that's wracked Syria since March 2011.
The state-run ITAR-Tass news agency said Clinton was blunt in her diplomatic challenge to Moscow.
"We have to be realistic," Clinton said. "We haven't seen eye-to-eye with Russia on Syria."
She made the remarks at the Asia Pacific Economic Cooperation summit and made a veiled criticism of a U.N. bid to rein in Syrian President Bashar Assad's military response to rebels.
"There is no point in passing a resolution with no teeth because we have seen time and time again that Assad will ignore it and keep attacking his own people," she said.
Clinton was attending a summit of the Asia Pacific Economic Cooperation.