The Cheetahs and Southern Kings will join the championship, that also includes teams from Wales, Ireland, Scotland and Italy, in time for the 2017-18 season.
The announcement ended weeks of speculation about the future of the two South African clubs, who were culled from the southern hemisphere's Super Rugby competition in the last month.
"It marks the start of a new adventure for rugby in South Africa with a number of exciting opportunities," SA Rugby chief executive officer Jurie Roux said in a statement.
The tournament will be split into two conferences of seven.
Each conference will be made up of two Welsh and two Irish teams, with one representative each from Scotland, Italy and South Africa.
The Bloemfontein-based Cheetahs join Irish clubs Connacht and Munster, Welsh sides Cardiff Blues and Ospreys, Glasgow Warriors from Scotland and Italy's Zebre in Conference A.
The Southern Kings, who are from Port Elizabeth, play in Conference B with Benetton (Italy), Dragons and Scarlets (Wales), Edinburgh (Scotland) and Irish sides Leinster and Ulster.
Each team will play 21 regular season games with three sides from each conference advancing to the end of season knockout stages. The final is on May 28.
The season begins next month and the fixtures will be released next week.
In order to provide travelling teams to South Africa with the best possible preparation, games will be fixed for Saturdays.
This will allow visiting teams to have a seven-day turnaround leading into these fixtures including five days that do not involve any travel.
For teams scheduled to play twice in South Africa, the aim will be for them to play back-to-back games on a single trip.
"It will not be without its challenges in aligning with a competition in a different part of the calendar and in very different playing conditions but it is also a fantastic opportunity for South African rugby to widen our playing horizons," Roux added.
It's been speculated that if the Cheetahs and Kings are successful in their transition, South Africa's four remaining Super Rugby teams might seek to play in European competitions when SANZAAR's broadcast deal expires in 2020.
