The prime minister says Bashar Assad's campaign of terror against the Syrian people must stop.
"The Assad regime has lost all legitimacy by killing its own people to stay in power," Harper said in a statement.
"I join with President Obama and other members of the international community in calling on President Assad to vacate his position, relinquish power and step down immediately."
Thousands have been killed or detained over the last five months as Syrians protest against the government.
Assad has told the United Nations chief that military operations in his country have ended, even as activists report more bloodshed and a high-level UN human rights team said Thursday the crackdown "may amount to crimes against humanity."
Harper's call for Assad to leave came after U.S. President Obama issued a stinging written statement urging the leader to quit. Obama said Assad's calls for reform ring hollow while he is "imprisoning, torturing and slaughtering his own people."
Obama's move was co-ordinated with the United Nations and with U.S. allies in Europe and the Middle East and followed an intense diplomatic campaign to increase pressure on Assad.
The European Union issued an identical call shortly after Obama's statement, followed quickly by similar words from the leaders of France, Britain and Germany.
President Nicolas Sarkozy of France — Syria's one-time colonial ruler — joined British Prime Minister David Cameron and German Chancellor Angela Merkel in expressing "utter condemnation of this bloody repression of peaceful and courageous demonstrators and the massive violations of human rights which President Assad and his authorities have been committing for months."
"They continue to cruelly and violently repress their people and flatly refuse to fulfil their legitimate aspirations," the three leaders wrote.
"They have ignored the voices of the Syrian people and continuously misled them and the international community with empty promises."
U.S. officials acknowledged the move is not likely to have any immediate impact on the Syrian regime's behaviour. But they said it would send a powerful signal that Assad is no longer welcome in the international community. And they noted that the additional sanctions would further boost pressure on Assad and his inner circle.
Every diplomatic lever is being pulled to increase the pressure, said Canada's Foreign Minister John Baird.
“I think we’re seeing an unprecedented diplomatic effort, obviously the Syrian people been very clear they don’t want other action that we’re taking in Libya so we’re seeing a decisive call for him to leave by a significant number of countries,” he told a news conference in Ottawa Thursday.
Last week, Canada expanded sanctions against Syria, though they are largely symbolic because exports to Syria are worth just $60 million dollars a year.