South African franchises Toyota Cheetahs and the Southern Kings will join an expanded Guinness Pro14 tournament in time for the 2017-18 season.
The tournament - 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 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," Celtic Rugby and the South African Rugby Union said in a joint statement.
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, Benetton Treviso and the Southern Kings will line up in Conference B.
Teams will play each other home and away in their own section and 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 Bloemfontein-based Cheetahs and the Southern Kings, from Port Elizabeth, will play only on Saturdays and there will be five travel-free days before matches.
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 Champions Cup.
The team with the highest points total outside of those six teams across both conferences will claim the final Champions Cup place.
"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," the Guinness Pro14 outlined.
"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.
"With a new format, new teams and new audiences the Guinness Pro14 - which leads World Rugby statistics for positive play - will hit even greater heights in 2017-18."
CEO of Rugby Players Ireland, Simon Keogh has said the organisation has been working closely with the IRFU in relation to the expansion.
"All player welfare issues, particularly those in relation to travel and temperature, have been taken into consideration and, while further details will be finalised over the coming weeks, the newly-formatted competition will not compromise player welfare," he said.
"The players are excited by the introduction of the two South African teams, and we will work to ensure that player welfare is at the heart of all aspects of operational planning given the short timeframe before the season commences."