Du Preez replaced Jean de Villiers, who returned home with the broken jaw he suffered in last the 46-6 win over Samoa.
“Fourie has been one of the best scrumhalves in world rugby for a long time, but he also understands the game better than most players and is a tactical genius,” coach Heyneke Meyer told a news conference on Wednesday.
“He will know exactly what is needed on Saturday when we continue our fight to keep our World Cup dream alive.”
Lock Victor Matfield, who was expected to take over from De Villiers as skipper, misses out with injury, his place taken by Lood de Jager.
De Villiers’s spot at centre went to Jesse Kriel, reuniting him with Damien de Allende in a young midfield combination that excited fans during the recent southern hemisphere Rugby Championship.
Bismarck du Plessis returns at hooker in place of Adriaan Strauss.
Flanker Willem Alberts, whose participation in the tournament has been in doubt because of a persistent calf injury, will get a chance to prove his fitness off the bench. Jan Serfontein, who only arrived in Newcastle on Monday to replace De Villiers, was included on the bench.
Meyer said his team would have to build on the victory over Samoa after losing to Japan in their opening game to stay on course for the quarter-finals.
“The performance against Samoa was much better, but Scotland have been impressive in their victories over Japan and the USA," he said.
“We know in which areas we have to improve and we will have to fire at 100 percent on Saturday against a motivated Scotland side.
The injuries have not been ideal, but we can’t do anything about that and the players selected will have to perform once again this weekend.”
Team: 1-Tendai Mtawarira, 2-Bismarck du Plessis, 3-Jannie du Plessis, 4-Eben Etzebeth, 5-Lood de Jager, 6-Francois Louw, 7-Schalk Burger, 8-Duane Vermeulen; 9-Fourie du Preez (captain), 10-Handre Pollard, 11-Bryan Habana, 12-Damian de Allende, 13-Jesse Kriel, 14-JP Pietersen, 15-Willie le Roux.
Replacements: 16-Adriaan Strauss, 17-Trevor Nyakane, 18-Frans Malherbe, 19- Pieter-Steph du Toit, 20-Willem Alberts, 21-Ruan Pienaar, 22-Pat Lambie, 23-Jan Serfontein.
(Reporting by Mark Gleeson; Editing by Ed Osmond; mark.gleeson@thomsonreuters.com; +27828257807; Reuters Messaging: Reuters Messaging: mark.gleeson.thomsonreuters.com@reuters.net)
