The uncapped Robbie Coetzee, Julian Redelinghuys, Nizaam Carr, Jaco Kriel and Seabelo Senatla - as well as the recalled Coenie Oosthuizen and Johan Goosen - join 29 players who were part of the Springboks' squad in the recent Rugby Championship.
Speaking during his squad announcement on Monday, South Africa coach Heyneke Meyer commented: "It's wonderful to have this kind of continuity in selection, while the five uncapped players in the squad have all been rewarded for superb form throughout the season.
"Many of the selected players were at our training camp in Stellenbosch last week where we put in a lot of very hard work. We'll have to hit the ground running when we assemble in Johannesburg on Wednesday before we depart on what will be a challenging tour.
"We start against the Six Nations champions [Ireland] in Dublin and then take on England, who have been on an upward curve over the last couple of years.
"Italy is always a tough customer at home and the Welsh have probably been one of the most consistent teams in the last number of seasons."
The depth of Meyer's squad will be tested in the final match of the tour against Wales in Cardiff on November 29.
That fixture falls outside the international Test window, meaning none of Meyer's overseas-based players will be available.
South Africa will also have to deal with a lengthy injury list, with the likes of Fourie du Preez, Schalk Brits, Pierre Spies and Flip van der Merwe ruled out.
Squad in full:
Forwards: Bakkies Botha, Schalk Burger, Nizaam Carr, Marcell Coetzee, Robbie Coetzee, Eben Etzebeth, Lodewyk de Jager, Jaco Kriel, Victor Matfield, Teboho Mohoje, Tendai Mtawarira, Trevor Nyakane, Coenie Oosthuizen, Bismarck du Plessis, Jannie du Plessis, Julian Redelinghuys, Gurthro Steenkamp, Adriaan Strauss, Duane Vermeulen, Warren Whiteley
Backs: Damian de Allende, Johan Goosen, Bryan Habana, Cornal Hendricks, Francois Hougaard, Patrick Lambie, Lwazi Mvovo, Ruan Pienaar, JP Pietersen, Handre Pollard, Cobus Reinach, Willie le Roux, Seabelo Senatla, Jan Serfontein, Morne Steyn, Jean de Villiers (captain)