"We cannot build peace with Assad," Foreign Minister Jean-Yves Le Drian said on French radio RTL.
"He cannot be the solution," said Le Drian, who was defence minister under the former Socialist government.
"The solution is to establish... a timeline for political transition that can lead to a new constitution and elections, and this transition cannot happen with Bashar al-Assad."
French President Emmanuel Macron said in July that the removal of the Syrian president was not a "prerequisite" for peace in the war-torn country, and that he did not see a "legitimate successor" to the leader who has been in power since 2000.
Paris had been a key supporter of the opposition to Assad's rule since the start of the conflict in 2011 which has since killed more than 320,000 people and displaced millions.
But Macron said that the fight against the Islamic State (IS) group was a priority for France, which has endured a string of terror attacks that have killed more than 230 people since 2015. Some of these were planned in Syria.
France's armed forces are in action as part of the US-led international coalition fighting IS in Syria as well as Iraq.
IS has lost much of the territory it controlled in the two countries, and thousands of its fighters have been killed since late 2014, when the coalition was set up to defeat the group.
- UN talks in October? -
Signup to our newsletter and follow us on Facebook and Twitter!
Le Drian said Friday that IS "will be defeated in Syria," leaving the country with a "single conflict, that of the civil war" pitting an opposition against the Assad government.
Macron has tasked Le Drian with forming a new contact group on Syria to relaunch the stalled political process.
So far Paris has not been forthcoming on the composition of the group, notably on the question of whether regional power Iran -- a key backer of the Syrian regime along with Russia -- would take part.
UN Syria envoy Staffan de Mistura said last month that he hopes to launch "real, substantive" peace talks between the government and a still-to-be-formed unified Syrian opposition in October.
De Mistura has hosted seven rounds of largely unsuccessful talks in Geneva, with Assad's fate one of the main obstacles to progress.
Kazakhstan has hosted parallel talks, with a new round possible in mid-September.
In May, Russia, Iran and Turkey -- a backer of the rebels -- agreed to establish safe zones across swathes of Syria.
The United States in July shut down a covert programme supporting armed Syrian opposition groups.
The head of the US military's special operations, Tony Thomas, denied that the four-year-old operation was scrapped as a way to placate Russia and earn its support for a ceasefire in southwestern Syria.