The two arrests are the result of investigations into Saturday night's shooting at a bar in the eastern city of Pietermaritzburg in KwaZulu-Natal province. Four people were killed and eight wounded when two men fired indiscriminately at customers.
The police ministry described the arrests in a statement as the beginning of holding "all those who orchestrated one of the country's bloodiest weekends" responsible.
It did not provide any further details.
Another 15 people, including two women, were shot dead early on Sunday in Soweto township, close to Johannesburg, in a separate incident.
Lirandzu Themba, a spokeswoman for the ministry, told AFP police believed those held were "linked" to the Pietermaritzburg shooting.
Shootings are common in South Africa, which has one of the world's highest murder rates, fuelled by gang violence and alcohol. But the two incidents over the weekend had left investigators puzzled.
"As a nation, we cannot allow violent criminals to terrorise us in this way, regardless of where such incidents may occur," President Cyril Ramaphosa said in a statement on Sunday.
