Just five of the fifteen selected played against the Boks the last time the sides met.
Robbie Henshaw will be starting at inside centre for Ireland against the World Champions on Saturday.
Conor Murray is set to earn his 100th Irish cap when he starts against South Africa at scrum-half with Jamison Gibson-Park named on the bench.
Murray is just one of just five players in the starting team that started the last game between the two sides in 2017.
Tadhg Furlong, Henshaw, Peter O’Mahony and Johnny Sexton were the other players to start against the Springboks five years ago.
Robert Baloucoune will line out on the wing while Garry Ringrose is set to start at outside centre.
The game at the Aviva Stadium will be Enniskillen native Baloucoune's third appearance in a senior Irish shirt.
37-year-old Johnny Sexton will captain Andy Farrell's side.
Former Ireland head coach and current Buccaneers boss, Eddie O'Sullivan says if Ireland can get the win against South Africa, they should win all their November series games.
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