"Once the ISIS threat has been reduced or eliminated, I think we can turn our attention directly to stabilizing the situation in Syria," he said.
"We're hopeful that we can prevent a continuation of the civil war and that we can bring the parties to the table to begin the process of political discussions."
The former ExxonMobil chief executive noted that holding such talks would require the participation of Syrian President Bashar al-Assad's regime along with its allies.
He narrowed his focus on key Damascus ally Moscow, with whom Washington has particularly frosty relations.
"We're hopeful that Russia will choose to play a constructive role in supporting ceasefires through their own Astana talks, but also, ultimately, through Geneva," Tillerson said.
"If we can achieve ceasefires in zones of stabilization in Syria, then I believe -- we hope we will have the conditions to begin a useful political process."
The top US diplomat insisted he had no concerns about possible Russian retaliation following an unprecedented US strike on a Syrian airfield this week.
"The Russians were never targeted in this particular strike," Tillerson said.
"It was a very deliberate, very proportional, and very targeted strike undertaken in response to the chemical weapons attack. And Russia was never part of the targeting."