Washington says it has proof Assad's forces used chemical weapons — including the nerve agent, sarin — against Syrian rebels.
Speaking in Paris alongside French President Francois Hollande, Harper said he accepts the U.S. claims.
"We share the view of our allies, I think, based on the evidence before us, that there have been uses of chemical weapons in Syria by the regime," Harper said in Paris.
"And as you know, the position of Canada on the regime is clear: we want to see Assad depart power and we want to see a regime that is representative of the entire population of Syria, which the Assad regime in its present form can never be."
The bloody civil war raging in Syria for two years — which has killed at least 93,000 people — will be at the top of the agenda at the coming meeting of the world's eight wealthiest countries in Northern Ireland.
G8 member Russia, which has so far resisted calls to oust Assad, on Friday disputed the U.S. claim that Assad's regime used chemical weapons against the rebels.
Russian President Vladimir Putin's foreign affairs adviser, Yuri Ushakov, said the evidence Russia has seen "didn't look convincing."
Ushakov added they is no talk yet of Russia supplying the S-300 air-defence missile systems to the Assad regime in retaliation to the U.S. arming the rebels.
Harper said he still has reservations about providing weapons and ammunition to the Syrian rebels.
"I think our concerns about the risks on both sides are shared also by our allies," the prime minister said.
The Syrian opposition must be clear about how it intends to use the weapons, Hollande said.
"We must exert some military pressure," he said.
"This is the reason why France, on a number of occasions, has set some principles while asking the Syrian opposition to be particularly clear as to its approach and the use of chemical weapons."
France has long known the Assad regime used chemical weapons, Hollande added.
"The White House has confirmed what France knew already, that is there are some chemical weapons and they have been used," he said.
"We must exert pressure on the regime of Bashar Assad. We must get him to understand that there is no other solution than a political solution. ... Assad must go."
— With files from The Associated Press
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