File Photo: South African President Cyril Ramaphosa delivers a speech on September 27, 2021. AFP
"We call upon all those countries that have imposed travel bans on our country and our southern African sister countries to immediately and urgently reverse their decisions," he said in his first address to the nation following last week's detection of the new variant.
Dozens of countries have blacklisted South Africa and its neighbours since South African scientists flagged Omicron last week.
"The prohibition of travel is not informed by science," Ramaphosa said.
"The only thing the prohibition on travel will do is to further damage the economies of the affected countries and undermine their ability to respond to, and recover from, the pandemic," he added.
"These restrictions are unjustified and unfairly discriminate against our country and our southern African sister countries".
Although the World Health Organization has defined Omicron, a variant of concern, scientists are still assessing its virulence.
Ramaphosa said the "most powerful tool" to limit its transmission was the vaccine and urged South Africans to get jabbed.
He said the government was considering making vaccines mandatory for certain activities and locations in a bid to increase uptake.
Just over 35 percent of adults in South Africa have been fully inoculated due to a slow start to its vaccine campaign and widespread hesitancy.
The country is the worst virus-hit in Africa, with around 2.9 million cases and 89,797 deaths reported to date.
Omicron is believed to be fuelling a rise in infections, with 1,600 new cases recorded on average in the past seven compared to 500 the previous week.