"Assad has an air force, and that air force is the cause of most of these civilian deaths as we have seen over the years and as we saw again in the last few days," Clinton said in a speech at the "Women in the World" summit in New York City. "And I really believe that we should have and still should take out his air fields and prevent him from being able to use them to bomb innocent people and drop sarin gas on them."
The former secretary of state and Democratic presidential nominee against Trump in 2016 reiterated her support for a no-fly zone over Syria and more direct support for protesters.
"I still believe we should have done a no-fly zone," she said, in a slight knock against former President Barack Obama, whose Cabinet she served in. "We should have been more willing to confront Assad."
US officials said Assad perpetrated the chemical attack this week that killed more than 70 people.
Trump said Thursday that "something should happen" with regard to Assad, after referring to the deadly attack as a "heinous" and "horrific" act against innocent people the previous day.
Meanwhile, Secretary of State Rex Tillerson said it appears that Assad should have "no role" in governing the Syrian people, and that "steps are under way" for the United States - along with an international coalition -- to remove the dictator.
"We are considering an appropriate response for this chemicals weapons attack," Tillerson said. "It's a serious matter. It requires a serious response."
Clinton, even as secretary of state, was a proponent of more direct action in Syria at the time, despite Obama's apprehension about military action in the country.
"I wish, obviously I wish that the international community writ large had been able to rein this in," Clinton said, while acknowledging that the decision was not an easy one.
The Obama administration asked Congress in August 2013 for authorization to launch a military strike on Syria. That vote never happened after a preliminary agreement was struck to remove chemical weapons from Syria.
In light of the recent chemical attack, that agreement now looks moot and Clinton nodded to the possibility that it could have failed on Thursday, saying that they believed at the time "we had gotten rid of their stock" of chemical weapons.
"Who knows whether they hid some or they bought more," she said. "We don't know. We just know the impact."
Clinton blamed Russia for backing Assad, arguing that Russian President Vladimir Putin "has basically weighed in, particularly with air power, to support this fight-to-the-death policy that Assad has."
And in a bit of psychological analysis, Clinton compared Assad and the Russian president.
"He is absolutely a prisoner of his family's expectations, his dead father's looming presence and his delusion, that I believe he now probably could pass a lie detector about, that everyone who opposes him is a terrorist," Clinton said of Assad, before adding, "That is how Putin thinks."
Clinton said that if she were in power, she would have told the Russians they were "either with us or against us on this no-fly zone."
"It is time," Clinton said, "the Russians were afraid of us because we were going to stand up for the rights, the human rights, the dignity and the future of the Syrian people."