The White House is considering launching military actions in Syria in response to an alleged nerve gas attack on by president Bashar Assad on his own people.
The Syrian leader should have "no role" to continue governing after the attack that killed at least 86, said Secretary of State Rex Tillerson in a press conference on Thursday.
He said that talks involving US leader Donald Trump and other allies were already "under way" over options for an international coalition to remove Mr Assad.
Mr Trump himself said that said what happened in Syria is "a disgrace to humanity" in comments to reporters aboard his Air Force One plane.
Asked if Assad should go, Mr Trump said: "He's there, and I guess he's running things so something should happen."
The president would not discuss what, if anything, the US might do in response to the deadly attack. He said it "shouldn't have happened, and it shouldn't be allowed to happen".
Talks between the Pentagon and the White House are already taking place over military options in Syria, an official speaking anonymously told the AP newswire.
Mr Trump, who has criticised his predecessor Barack Obama for failing to enforce a 'red line' over chemical attacks in Syria, said he had not yet briefed lawmakers on military options.
However Mr Tillerson made it clear that the US considered that Assad's forces were guilty of using banned weapons and no longer believed his position to be viable.
Assad's role in the future is uncertain, clearly, and with the acts he has taken, it would seem that there would be no role for him to govern the Syrian people.
When asked if he and Mr Trump would organise an international international coalition to remove Mr Assad, he replied: "Those steps are underway."
Mr Trump said that he had not spoken with the Russian leader and key Assad ally Vladimir Putin since Tuesday's alleged chemical attack in Idlib but added "at some point I may".
Russia is seen by many as a potentially crucial player in the Syrian conflict, after launching airstrikes in support of Assad's forces that have reshaped the conflict in favour of government troops.
Meanwhile Turkey's president Tayyip Erdogan said they would welcome US action to oust Assad and would be willing to play a role, according to media.
"If a (US) action will really be put forward, we are ready to do our part," Mr Erdogan reportedly told an interview with broadcaster Kanal 7.