Wiese was a late withdrawal from the side that lost 30-26 to France last weekend, having failed to recover from a concussion suffered in the 19-16 defeat by Ireland the week before.
He replaces Kwagga Smith (29), while Salmaan Moerat (24) and Marvin Orie (29) make up the second row with Eben Etzebeth (31) rested on the bench and Franco Mostert (31) moving to flank in place of Pieter-Steph du Toit (30).
The only change in the back line sees Andre Esterhuizen (28) come in at inside centre, with Damian de Allende (30) moving to outside in place of Jesse Kriel (28).
"A couple of players have been training very hard in the last few weeks and deserve a chance to start," Nienaber said in a media release from South African Rugby.
"Salmaan and Marvin are both Stormers players, so they have been playing together for a while, and they are very hungry for game time, so we are looking forward to what they bring in the game.
"It’s also good to have Jasper back against the physical Italian pack, and we know that Kwagga will spark something different when he takes the field.
"Evan (Roos) also gets a chance off the bench and his skills will work well with Kwagga’s in the loose trio."
South Africa are hoping to avoid a third successive defeat and come up against a resurgent Italy who shocked Australia with a 28-27 win last weekend.
Italy have had some past joy against the Springboks, beating them for the first time 20-18 in Florence six years ago.
Team: 15 – Willie le Roux, 14 – Cheslin Kolbe, 13 – Damian de Allende, 12 – Andre Esterhuizen, 11 – Kurt-Lee Arendse, 10 – Damian Willemse, 9 – Faf de Klerk, 8 – Jasper Wiese, 7 – Franco Mostert, 6 – Siya Kolisi (captain), 5 – Marvin Orie, 4 – Salmaan Moerat, 3 – Frans Malherbe, 2 – Bongi Mbonambi, 1 – Ox Nche
Replacements: 16 – Malcolm Marx, 17 – Steven Kitshoff, 18 – Vincent Koch, 19 – Eben Etzebeth, 20 – Kwagga Smith, 21 – Evan Roos, 22 – Cobus Reinach, 23 – Manie Libbok
