Cheetahs boss Harold Verster has described South African participation in an expanded Guinness PRO14 tournament as "a whole new ball game" for rugby in the country.
South African franchises Toyota Cheetahs and the Southern Kings will see the former PRO12 increased by two teams in time for the 2017-18 season.
The competition - which will be renamed the Guinness PRO14 Championship - 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The Bloemfontein-based Cheetahs and Southern Kings, who play in Port Elizabeth, had already withdrawn from next year's Super Rugby tournament.
"There will be a steep learning curve for our coaches and players, but we are in it to win it," Cheetahs chief executive Verster told www.sarugby.net.
"This is a whole new ball game for rugby in South Africa, and we are proud to be trailblazers. There is a lot of excitement around the union about the opportunity, and we are already looking forward to kick-off.
"The Free State is one of the great nurseries of rugby in South Africa, and this is an exciting prospect for our young players - to test themselves against top players from the northern hemisphere."
Eastern Province Rugby Union president Andre Rademan added: "The Kings have been through tough times on and off the field over recent years, but we now have the chance to reclaim our status as one of the powerhouses of South African rugby.
"Under difficult conditions and against an unsettled off-field environment, the Southern Kings have been on an upward playing curve this season, and there is much to be excited about.
"This team represents the heartlands of black rugby in South Africa - a tradition stretching back to the very establishment of the game in this country - and we will bring a unique passion and flavour to the tournament."
The groups have been based on last season's results, with the Ospreys, Cardiff Blues, Munster, Connacht, Glasgow, Zebre and the Cheetahs in Conference A.
Last season's champions Scarlets, Dragons, Leinster, Ulster, Edinburgh, Treviso and the Southern Kings will line up in Conference B.
Teams will play each other home and away in their own section and face sides out of their own conference once.
The 21-game season will be completed by two additional rounds of matches, ensuring Welsh and Irish teams retain their current six derbies each. The Scottish, Italian and South African sides will play each other three times.
The Cheetahs and the Southern Kings will play only on Saturdays, and there will be five travel-free days before matches, while the South African franchises will not be able to qualify for Europe through their league placing.
The top three non South-African sides from each conference will qualify for the European Champions Cup, and the team with the highest points total outside of those six teams across both conferences will claim the final Champions Cup place.
Celtic Rugby and the South African Rugby Union said in a joint statement: "The agreement means that the Championship will take place across the northern and southern hemispheres and marks the first phase of expansion as the Guinness PRO14 becomes a truly global tournament,.
"This move will contribute to the drive for ever higher standards that we demand across the tournament and provide greater resources to our clubs who will compete in the most testing environment the Championship has ever created.
"We can also reassure supporters across the Championship that all current home and away derby games have been protected - these fixtures are sacrosanct to the tournament, and those tribal rivalries are just one element of what makes the Guinness PRO14 so special."
The full fixture list will be issued by Guinness PRO14 in the near future.