Hillary Clinton called for the United States to "take out" Syrian government-controlled airfields just hours before Donald Trump launched air strikes against Bashar Assad's regime.
Speaking in her first public interview since losing the US election in November last year, Mrs Clinton said Mr Assad's aerial power had been the key component behind widespread civilian deaths since the start of the civil war in 2011.
President Trump launched a barrage of cruise missiles in the early hours of Friday morning on a Syrian air base thought to be behind this week's chemical weapons attack.
Speaking to the New York Times columnist Nicholas Kristof, Mrs Clinton said she believed the US had been wrong not to have previously launched such an offensive.
She said: "Assad had an air force, and that air force is the cause of most of the civilian deaths, as we have seen over the years and as we saw again in the last few days.
"And I really believe that we should have and still should take out his airfields and prevent him from being able to use them to bomb innocent people and drop Sarin gas on them."
Tuesday's chemical attack on Idlib province in northern Syria drew the ire of several United Nations member states and received widespread condemnation across the globe.
More than 72 people are thought to have died in the attack, which is believed to have constituted a mix of chlorine gas and the deadly nerve agent Sarin.
However, America's retaliatory strike was angrily condemned by Russia, Assad's principal international backer, as an "aggression against a sovereign state in violation of international law".
Friday's offensive, in which 59 missiles were launched from two US navy warships in the Mediterranean sea, marks the first time America has directly intervened in the conflict.
Asked by Mr Kristof if she felt not acting more decisively on Syria had been her gravest foreign policy mistake, Mrs Clinton said she had been aware the conflict could become "one-sided" in the first stages of the Syrian conflict.
She said: "When I was secretary of state I teamed up with Dave Petraeus, then director of the CIA, Leon Panetta, then secretary of defence, to present a plan for us to move more aggressively to support protesters to provide some back up in what I thought could turn out to be a very one-sided battle.
"This was before Isis really came to public awareness with their plan for a caliphate and their setting up of headquarters in Raqqa.
"I believed then, and I've said this repeatedly, I believe we should have done more at that point."
Despite Barack Obama warning that a chemical weapons attack would mark the crossing of a red line in 2012, his administration ultimately pulled back from proposals to launch an offensive when reports of a deadly Sarin attack emerged in August 2013.
In an emotional speech announcing the offensive on Friday, President Trump spoke of the "barbaric" chemical attack in which at least 20 children died.
"Using a deadly nerve agent, Assad choked out the lives of helpless men, women and children. It was a slow and brutal death for so many," he said.
"Even beautiful babies were cruelly murdered in this very barbaric attack.
"Tonight, I ordered a targeted military strike on the airfield in Syria from where the chemical attack was launched.
"It is in this vital national security interest of the United States to prevent and deter the spread and use of deadly chemical weapons.
"There can be no dispute that Syria used banned chemical weapons."
Downing Street later said that it "fully supports" the US action.
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