In an historic fixture to mark the opening of Leicester's new gigantic Caterpillar stand, the English Champions recorded a thrilling 22-17 victory.
Scrum-half Ben Youngs was the hero for Leicester, kicking 17 points in an impressive individual performance.
Argentina wing Lucas Amorosino's brilliant solo try saw Leicester lead 16-11 at the break and they never looked back.
Cheetahs flyer Jongi Nokwe scored early for the Boks but star fly-half Ruan Pienaar kicked six points fewer than the livewire Youngs.
And while the World Champions left their entire first-choice XV back in South Africa for a further week's training ahead of next Friday's clash with France, the Tigers were missing a whole host of players themselves.
Richard Cockerill was without the likes of 2009 Lions Tom Croft and Harry Ellis, 2005 tourists Julian White and Lewis Moody and England starters Jordan Crane, Louis Deacon and Dan Hipkiss, as well star names such as Marcos Ayerza, Anthony Allen, Toby Flood, Ben Kay, Geordan Murphy, Alesana Tuilagi, Sam Vesty and Ben Woods.
And even a Bok second team featured eight players who received game time in the three-match series against the Lions earlier this summer.
Odwa Ndungane, Wynand Olivier, Nokwe, Pienaar, Guthro Steenkamp, Danie Rossouw, Andries Bekker and captain Chilliboy Ralepelle all faced the Lions for their country and had been looking to press their claims for inclusion against France, Italy and Ireland over the coming month.
"That's right up there as a career highlight for me," said Tigers skipper Aaron Mauger, a former All Black legend who regularly played against the Springboks and tasted a series triumph over the Lions four years ago.
"It's pretty special. They are World Champs and we had to respect them but not be in awe of them.
"There wasn't a lot of expectation from anyone but ourselves. But we had the belief that we could win and, if you have that, you can do anything."