Kolbe, better known for runs down the wing, suffered a broken jaw against Wales in July and returns in a surprise switch by the Springboks, who start the first of four November internationals in Europe.
Kolbe replaces Willie le Roux (33) from the side that beat Argentina 38-21 in the Rugby Championship in September with Nienaber making a further two backline changes but keeping the same pack.
Damian Willemse (24) will be the fly half after missing the last test, replacing veteran Frans Steyn (35), while Kurt-Lee Arendse (26) is on the wing for the injured Canan Moodie (19).
"Damian has done well for us at fly half, and he is continuing to grow as a player in that role, while we think Cheslin has the potential to add a new dimension to our game at full back," Nienaber told a virtual news conference.
"He was sidelined for a while after breaking his jaw against Wales, but he has played four 80-minute matches for Toulon since returning to play, and we are confident that he will step up to the challenge."
Nienaber said he expected Ireland to be a major challenge, particularly at home.
"Ireland are the top ranked team in the world currently and they've shown in the past that they can be a force to be reckoned with in Dublin," he said.
"Obviously we are a long way out from the World Cup, but we have a limited number of matches left before the competition and the preparation doesn't get better than playing a side we will face in the World Cup and the number one side in the world.
"This match is important for us for many reasons, one of which is to test our player combinations with the World Cup less than a year away," he added.
