In an interview with CBS News, Mr Kerry said the US is pushing for Assad to discuss seriously a transition strategy to quell the Arab country’s four-year civil war.
Mr Kerry said: “We have to negotiate in the end.”
While previous efforts saw Assad’s government not engage on a concrete plan, Mr Kerry said the US is trying “to get him to come and do that”.
He said that may require additional pressure on Assad’s Iran-backed government, which is fighting Sunni rebels and “Islamic State” (IS) extremists.
Mr Kerry said there may need to be “increased pressure on him of various kinds” to get talks to happen. “We’ve made it very clear to people that we are looking at increased steps that can help bring about that pressure,” he said.
Representatives of the Syrian government took part in talks in Moscow in January with opposition figures, although the main western-backed opposition group shunned the conference.
The nearly four-year conflict has claimed over 200,000 lives, displaced a third of Syria’s population, and nurtured the extremist IS group, which now holds a third of both Syria and neighbouring Iraq in its self-declared caliphate.
Mr Kerry said negotiations are important “because everybody agrees there is no military solution; there’s only a political solution”.
“But to get the Assad regime to negotiate, we’re going to have to make it clear to him that there is a determination by everybody to seek that political outcome and change his calculation about negotiating. That’s under way right now.”
Meanwhile, there is evidence that IS group used chlorine gas as a chemical weapon against peshmerga fighters, Kurdish authorities in Iraq said.
The allegation by the Kurdistan Region Security Council in relation to a suicide truck bomb attack in northern Iraq on January 23 has not yet drawn a reaction from IS, which holds a third of Iraq and neighbouring Syria in its self-declared caliphate.
However, Iraqi officials and Kurds fighting in Syria have made similar allegations about the militants using the low-grade chemical weapons against them.
In a statement, the council said the alleged chemical attack took place on a road between Iraq’s second-largest city, Mosul, and the Syrian border, as peshmerga forces fought to seize a vital supply line used by the Sunni militants.
It said its fighters later found “around 20 gas canisters” that had been loaded onto the truck involved in the attack.
Video provided by the council showed a truck racing down a road, with white smoke pouring out of it as it came under heavy fire from peshmerga fighters. It later showed a white, billowing cloud after the truck exploded.
An official with the Kurdish council told reporters that dozens of peshmerga fighters were treated for “dizziness, nausea, vomiting and general weakness” after the attack.
The Kurds say samples of clothing and soil from the site were analysed by an unnamed lab in an unnamed coalition partner nation, which found chlorine traces.