The Springboks, who rested several regulars for the fixture with an eye on Ireland in Dublin next weekend, scored four tries to one in what will go down as a brave performance in which they were at one stage down to 13 players.
Number eight Marco van Staden, and scrumhalves Morne van den Berg and Grant Williams, and centre Ethan Hooker crossed for tries for the visitors, while fullback Ange Capuozzo got the only Italian score.
The home side will see it as a huge opportunity missed, but were wasteful when they did get into the South African 22 and also came up against some stout Springbok defence.
For the second week in a row, South Africa lost a lock to a permanent red card when Franco Mostert’s tackle on Italy fly-half Paolo Garbisi that referee James Doleman deemed always illegal with no attempt to wrap in the tackle.
South Africa will have plenty of evidence to contest the red, including whether there was head contact at all, with replays suggesting it was shoulder on shoulder at worst.
Last week in Paris it was Lood de Jager, this week they lost Mostert after just 11 minutes on the clock.
“We went through it last weekend and this week again. We make plans in the game as we go, because we know things happen,” Springbok captain Siya Kolisi said.
“There are always stumbles along the way and that is what I am grateful for in our coaching staff, they are always making plans for every scenario.
“It is not easy on us, we can talk about sacrificing (for the team) but to see a guy like Sous (Mostert) sitting there, we can see the hurt in his eyes.
“I love the way this team is able to stand up and fight and we always say that within those four lines we can always go as hard as we can and control what we can.”
It also meant early afternoons for flanker Ben-Jason Dixon, and props Zachary Porthen and Boan Venter, as coach Rassie Erasmus brought on Ruan Nortje, Wilco Louw and Gerhard Steenekamp to add experience and grunt in the scrum.
Italy had the ascendency at the scrum despite the changes as the Springboks struggled in an area where they are usually so strong.
Garbisi missed two penalties inside the first half-hour, with the Springboks making a fourth change on 26 minutes as hybrid flanker/centre Andre Esterhuizen came on for wing Edwill van der Merwe.
It took South Africa half an hour to get into the Italy 22, and after a succession pick-and-goes came to nothing, Pollard kicked a penalty from in front of the posts to give the visitors a tenuous 3-0 lead.
When Italy pushed the Springboks off their own ball at the scrum, Garbisi made it third time lucky from the tee to level the scores via a penalty.
The Springboks made a second entry into the Italy 22 on the stroke of halftime and scored points again, this time a try as Van Staden crashed over from close range with support from his fellow forwards.
Italy won a penalty early in the second period and Garbisi had a simple kick to close the gap to four points.
The Springboks were dealt a further blow when Van Staden cynically went off his feet to stop quick ball on an Italian attack in the visitors’ 22 to give away and penalty and earn a yellow card to leave South Africa with 13 players for the next 10 minutes.
Garbisi knocked over the penalty and suddenly the Springboks had just a single point lead at 10-9.
The Springboks won a penalty almost straight from the kick-off and Pollard put the ball between the posts.
Italy were reduced to 14 players when Lorenzo Cannone was too upright in the tackle against Kwagga Smith and he was sent to the sin-bin.
The Springboks used the penalty to work their way into the Italian half and after Italy infringed at the ruck, the visitors took the scrum, from which Van den Berg crossed near the posts and South Africa led 20-8 with an hour gone.
But Italy would not give up and hit back with their first try as Capuozzo ran a brilliant angle to collect and race past some South African forwards to score.
That might have tilted the momentum in Italy's favour with the next score vital, and it came the way of South Africa with a brilliant run by Canan Moodie down the left wing, beating defenders before feeding the ball inside for Williams to run in under the posts.
The final score came on the hooter when Manie Libbok's cross-kick was perfect for Hooker to collect and score.
