Fijian flavour for Azzurri
Vunisa, who has yet to play for Italy after being called into the squad for the November Tests, will replace Simone Favaro in the loose trio after the Treviso player suffered a sore neck in training.
In the only other notable switch, Leonardo Sarto has been pulled back to the right wing with Luke McLean going the other way to the left wing.
Italy beat Samoa 24-13 in their opening Test and despite last week's 20-18 defeat to the Pumas, coach Jacques Brunel said he had seen enough to confirm the nucleus of his team for the Springboks, which he described as "the form team of the November series".
"After the first two games against Samoa and Argentina we were satisfied at how the team performed so we thought it was only fair to confirm the line-up that has impressed in recent weeks," said Brunel.
On Vunisa's inclusion, Brunel added: "We'd been following Sam for the past year and a half, first of all with Calvisano and now with (current club) Zebre.
"Now it's time we tested him at international level."
Brunel, however, said the powerful Fijian had a lot to live up to.
"Against Samoa and Argentina Simone made a brilliant return to competition after more than a year away from the international matches," added the Frenchman.
South Africa, who suffered a 29-15 loss to Ireland in their opening Test in Dublin, made amends with a 31-28 win over England at Twickenham last week.
They are expected to claim what would be their 12th consecutive win over the Azzurri at Padua's Stadio Euganeo.
"The Springboks are without doubt the form team of this November series. They had a great summer and also brought the All Blacks' winning streak to an end," said Brunel.
Italy will be hoping Vunisa follows in the footsteps of fellow recent debutant Kelly Haimona by impressing on his maiden appearance for the Azzurri.
New Zealand-born flyhalf Haimona kicked 14 points ion the win over Samoa and scored 15 with the boot in a 20-18 loss to the Pumas last week.
Haimona's promising displays have also relegated Perpignan flyhalf Tommaso Allan down the pecking order.
Allan was sent home from a training camp earlier on Thursday.
"As regards Allan, he was given opportunities during the course of last season. It's only fair we give Haimona the same chance now," added Brunel.
