The Springboks raced into a 20-0 lead but allowed themselves to be pinned back for the first 20 minutes of the second half before scoring three tries in the final quarter-hour.
All but one of the tries came from the hosts' speedy back line in an error-filled match in which Italy surprised the hosts with their resilience and tactic of keeping the ball in hand.
Hooker Adriaan Strauss scored first for South Africa after 14 minutes with a pushover try before a second was added nine minutes later as JJ Engelbrecht dotted down after a spectacular break from Bryan Habana whose pace caught the Italians cold.
The comfortable halftime cushion set up the possibility of a runaway win but Italy were a changed outfit after the break, taking the game to South Africa and pinning the home side in their own half.
Alberto Sgarbi's try after an audacious pass through his legs from Italian skipper Sergio Parisse was richly deserved and when debutant fly half Alberto di Bernardo slotted over a penalty just before the hour mark, the Italians had reduced the deficit to just 10 points.
Home crowd frustration boiled over with a bout of jeering when flyhalf Morne Steyn kicked away possession but the last 15 minutes suddenly saw the Boks revive their form.
Habana scored his 48th test try as he collected a ball just inside the Italian half and then set off at pace, cutting through the defence spectacularly to score.
That was followed by two more tries from the backline with captain Jean de Villiers scoring at the end of an expansive move and Bjorn Basson added a fifth with an intercept try from the halfway line.
"We had a slump in the middle of the game but come back strongly in the latter part of the second half," De Villiers said in a pitch-side interview.
"The substitutes made a major difference when they came and that's what you want, for all 23 players to play their part."
The match was the second of a double-header in Durban on Saturday, with Samoa beating Scotland 27-17 in the earlier fixture.
