Abd sl-Halim Khaddam told the Arabic newspaper Asharq al-Awsat that he was rallying Syrian opposition parties to "create the right atmosphere for the Syrian people to topple the regime".
In an interview from his home in Paris on Friday he said: "This regime cannot be reformed, so there is nothing left but to oust it. The Syrian people will be the ones to oust it."
Khaddam's remarks were the latest salvo in an unprecedented verbal attack against Bashar al-Assad, the president of Syria.
Al-Assad is under increasing international pressure to co-operate with a UN inquiry into the assassination of Rafiq al-Hariri, the former Lebanese prime minister who died in a bombing in Beirut last February.
Change from within
Khaddam said he was not seeking to become president, but admitted to political aspirations. "I want to save the country," he said.
Asked if he would seek help from foreign governments to end al-Assad's rule, Khaddam said: "I did not contact anybody because change has to come from within. If the main vector for change is external, then the interests of the country are harmed."
Last week, Khaddam accused al-Assad of being an authoritarian ruler of a corrupt government and said in a television interview that al-Assad had threatened al-Hariri a few months before he was killed.
Syrian politicians have accused him of treason for criticising the president. On Thursday, the government froze the assets of Khaddam and his family.