As well as Botha, there are two other Irish-based players in the Springboks' 22, with Leinster prop CJ van der Linde and Munster centre Jean de Villiers selected on the replacements bench.
Meanwhile, Victor Matfield returns in the second row, replacing Andries Bekker and linking up once again with Bakkies Botha.
Schalk Burger is back at openside flanker with Danie Rossouw moving to number 8. There is one change to the back-line with Wynand Olivier starting at inside centre in place of the injured Adi Jacobs.
There are four more changes on the bench - front rowers Bismarck du Plessis and van der Linde return from injury, while Jean de Villiers is recalled and uncapped flanker Dewald Potgieter is included in a 'Boks matchday squad for the first time.
South African skipper Smit will equal Percy Montgomery's record as the most-capped Springbok against Ireland (six caps), while Jaque Fourie will equal Jean de Villiers' record as the most-capped Springbok centre.
SOUTH AFRICA TEAM & REPLACEMENTS (v Ireland, GUINNESS Series 2009, Croke Park, Saturday, November 28, kick-off 2.30pm):
15 - Zane Kirchner (Blue Bulls)
14 - JP Pietersen (Sharks)
13 - Jaque Fourie (Lions)
12 - Wynand Olivier (Blue Bulls)
11 - Bryan Habana (Blue Bulls)
10 - Morne Steyn (Blue Bulls)
9 - Fourie du Preez (Blue Bulls)
1 - Tendai Mtawarira (Sharks)