Police Minister Bhiki Sele said the youngest victim was 13 of at least 21 people who died at the site of drinking over the weekend.
The cause of the deaths was not immediately clear, and officials were investigating. Victims were found scattered on the floor and tables at Enobeni Tavern in the City of East London.
The bodies were taken to the mortuary, where a post-mortem will be conducted.
Mr Cele, who visited the scene and was briefed by local police, said the dead were between 13 and 17 years old – but a detailed list of victims had not yet been drawn up. The legal minimum age for drinking in South Africa is 18 years.
Reports show those who went to the inn were celebrating the end of school exams. South African President Cyril Ramaphosa expressed his “deepest condolences” to the victims’ families.
“This tragedy is made even more grave by its occurrence during Youth Month – a time during which we… advocate and advance opportunities for improved socio-economic conditions for the youth of our nation,” he said in a tweet.
Oscar Mabuyane, premier of East Cape Province where the tragedy happened, did not give possible reasons for the deaths but condemned the “unlimited consumption of liquor”.
He said at the scene: “You can’t just trade in the middle of society like this and think that young people are not going to experiment.”
The incident happened in the early hours of Sunday. A provincial security official told AFP news agency that a stampede had been ruled out as the cause of death because “no wounds were visible”.