Etzebeth, a major ‘enforcer’ in the Springbok pack, had been struggling with a shoulder problem picked up in the 18-3 victory over Scotland, but will line up alongside Franco Mostert in the second row.
It is the same starting XV that defeated the Scots, bar Bongi Mbonambi at hooker as he replaces Malcolm Marx, who has since been ruled out of the tournament with a knee injury.
Deon Fourie and Marco van Staden are the replacement hooker options, while the Munster lock pairing of RG Snyman and Jean Kleyn are also on the bench.
"It’s going to be a grind of a match and we need to pitch up physically and mentally. We also need to start with intensity and stay focused until the final whistle," Nienaber said.
"This is a massive game for both sides with an eye to progressing out of our pool, so we need to be extremely accurate in all areas of our game."
The Boks used a 7-1 split between replacement forwards and backs when they inflicted a record 35-7 defeat on New Zealand in a warm-up game in London last month.
On that occasion it was explained by the late withdrawal of back Willie le Roux due to injury, but it proved highly effective in subduing the All Black forward threat for the full 80 minutes.
The Boks were criticised when they introduced a 6-2 split to win the World Cup in 2019, and their move to 7-1 has re-ignited that debate, with some pundits feeling it is against the spirit of the game.
The lone back on the bench is scrumhalf Cobus Reinach, who can also play on the wing, though loose-forward Kwagga Smith is a former stalwart of Sevens rugby and has featured in the backline before.
Flyhalf Handre Pollard, who joined the squad on Monday as a replacement for Marx, was not considered for this game.
"Ireland are a quality team with a strong pack of forwards and talented backs, and they play with a lot of speed," said Nienaber.
"We faced them late last year (a 19-16 loss in Dublin) and we’ve been keeping an eye on their performances, so everyone knows what we have to do this weekend."
Team: 15-Damian Willemse, 14-Kurt-Lee Arendse, 13-Jesse Kriel, 12-Damian de Allende, 11-Cheslin Kolbe, 10-Manie Libbok, 9-Faf de Klerk, 8-Jasper Wiese, 7-Pieter-Steph du Toit, 6-Siya Kolisi, 5-Franco Mostert, 4-Eben Etzebeth, 3-Frans Malherbe, 2-Bongi Mbonambi, 1-Steven Kitshoff
Replacements: 16-Deon Fourie, 17-Ox Nche, 18-Trevor Nyakane, 19-Jean Kleyn, 20-RG Snyman, 21-Marco van Staden, 22-Kwagga Smith, 23-Cobus Reinach.
