Lambie, who came on for the second half of South Africa's 22-17 win over England in Durban, replaces the injured Zane Kirchner.
"Pat's a great player and still very young - people forget he's just 21. He brings something different, more attacking options, and he had a superb second half last week," Springboks coach Heyneke Meyer told a news conference.
"In training, he's shown some brilliant touches in attack.
"He's very good under the high ball and very good defensively even though he's not very big, so we won't lose much and I'm very confident he will do well," Meyer added.
Tighthead prop Kruger comes in for Coenie Oosthuizen, who suffered a neck injury last weekend that will keep him out of the rest of the series. Basson takes Lambie's place on the bench.
"I wanted to keep some continuity in the team because they played reasonably well last week and there are a lot of youngsters who will now know the game plan better," Meyer said.
Team - 5-Pat Lambie, 14-JP Pietersen, 13-Jean de Villiers, 12-Francois Steyn, 11-Bryan Habana, 10-Morne Steyn, 9-Francois Hougaard, 8-Pierre Spies, 7-Willem Alberts, 6-Marcell Coetzee, 5-Juandre Kruger, 4-Eben Etzebeth, 3-Jannie du Plessis, 2-Bismarck du Plessis, 1-Tendai Mtawarira. Bench: 16-Adriaan Strauss, 17-Werner Kruger, 18-Flip van der Merwe, 19-Keegan Daniel, 20-Ruan Pienaar, 21-Wynand Olivier, 22-Bjorn Basson.