The three-in-one combination anti-retroviral (ARV) was secured at a record-low price and will cost the state 89 rand a month ($10, eight euros) per patient.
"Before 2010, we were buying the most expensive ARVs in the world. Now we are a country where the ARVs are the cheapest in the world," said Health Minister Aaron Motsoaledi.
"It means we can increase the number of people on treatment," he added during a visit to the township of Ga-Rankuwa, about 35 kilometres (22 miles) northwest of the capital Pretoria.
After years of refusing to roll out ARVs, South Africa now has 1.9 million people on treatment among its 5.6 million HIV-positive population, which is the world's largest.
The new pill will be introduced this month to positive pregnant women and breastfeeding mothers, people co-infected with TB, and to new ARV patients.
Patients already on treatment will be assessed by doctors to start switching later this year.
"You're just going to take it once, and it's just going to be less pill burden," said patient Andrew Mosani.
"People are tired (of) taking many drugs on a day to day basis."
The pill also had fewer side effects and was easy to swallow, he added.
The South African National AIDS Council welcomed the treatment shift, saying it hoped it would encourage patients to stay on treatment.
"This is simplifying the way patients have become used to taking ARV treatment," said the council's CEO Fareed Abdullah.
"We have come a very long way since the advent of anti-retrovirals. At one point, patients used to take up to 16 pills a day," he added.
South Africa once refused to roll out ARVs under former president Thabo Mbeki but now has the largest anti-retroviral (ARV) programme in the world.
The scaling up of treatment has seen the number of pregnant women passing on HIV to their babies brought down to less than three percent.
Life expectancy has also shot up by six years to 60 over the past few years.