Ireland drop captain O'Mahony to bench for Springboks rematch
His loose forward place is taken by Tadhg Beirne, who operated as a lock when the Six Nations champions lost the first Test 27-20 in Pretoria last weekend.
Head coach Andy Farrell has made four personnel changes - three enforced by injuries - and two positional to the first Test starting line-up.
Injuries sustained in Pretoria ruled out inside centre Bundee Aki (shoulder), scrum-half Craig Casey (concussion) and hooker Dan Sheehan (knee).
Robbie Henshaw moves from outside to inside centre to take over from Aki, and will be partnered in midfield by Garry Ringrose, a first Test substitute.
Veteran Conor Murray replaces Casey, Ronan Kelleher comes in for Sheehan and James Ryan, who will form the second row with Joe McCarthy, takes over from O'Mahony.
The positional switches involve Henshaw and Beirne, who last played in the back row at the 2023 World Cup in France, where Ireland lost to New Zealand in the quarter-finals.
Henshaw, full-back Jamie Osborne and winger James Lowe also suffered injuries in a bruising Pretoria showdown, but have been cleared to play at Kings Park stadium in the Indian Ocean city.
Props Cian Healy and Finlay Bealham retained their places on the bench, as do loose forward Ryan Baird and utility back Ciaran Frawley.
In come back Stuart McCloskey, scrum-half Caolin Blade and hooker Rob Herring, and O'Mahony completes the bench.
Ireland must win to share the series and avoid a series defeat for the first time in South Africa.
The second Test was highly anticipated long before Ireland arrived in the republic with the 52,000 tickets selling out in less than one hour.
Victory for the Springboks in Pretoria, where each team scored three tries, snapped a three-match losing streak against the Irish.
While Farrell has had to contend with numerous injuries, South African counterpart Rassie Erasmus named an unchanged matchday 23 led by Siya Kolisi on Tuesday.
Ireland team
Starting XV: 15 Jamie Osborne, 14 Calvin Nash, 13 Garry Ringrose, 12 Robbie Henshaw, 11 James Lowe, 10 Jack Crowley, 9 Conor Murray, 8 Caelan Doris (c), 7 Josh van der Flier, 6 Tadhg Beirne, 5 James Ryan, 4 Joe McCarthy, 3 Tadhg Furlong, 2 Ronan Kelleher, 1 Andrew Porter
Replacements: Rob Herring, Cian Healy, Finlay Bealham, Ryan Baird, Peter O'Mahony, Caolin Blade, Ciaran Frawley, Stuart McCloskey
