With regular number eight Billy Vunipola injured and Nathan Hughes suspended, Jones had been expected to go for uncapped Zach Mercer, who was instead named among the replacements as tough-tackling Wilson wins his fifth cap and his second start.
Brad Shields wins his third cap at blindside with four-cap Tom Curry, impressive in the 2-1 series defeat against the Springboks, keeping the number seven shirt.
As expected, Owen Farrell will start at flyhalf, with Ben Te'o, who has played only 25 minutes of club rugby this season, and Henry Slade outside him and George Ford on the bench.
Dylan Hartley, co-captain with Farrell, returns at hooker alongside props Kyle Sinckler and Alec Hepburn, who makes his first international start after two appearances off the bench.
Elliot Daly is fullback with Jonny May and Jack Nowell claiming the wing berths as Chris Ashton failed to make the matchday squad.
Mark Wilson will start for England.
Image credit: Eurosport
Manu Tuilagi, who last played for England in 2016 and who has endured a wretched four-year run of injuries, is named on the bench along with uncapped prop Ben Moon. Currently on the last day of the team’s warm-weather training camp, Jones said in a statement: "We’ve become very well organised in our set piece and have done a lot of good work in Portugal over the last week.
"We have put in a new defence system and our attack looks more organised than it was on the South Africa tour." England lost the first two games on that trip in June, despite racing to early leads in both on the back of some scintillating play, before winning the third.
The Springboks, who were superb in beating the All Blacks in Wellington then agonisingly losing the home return in the Rugby Championship last month, will be without several key players on Saturday as the test falls outside the international window meaning clubs are not obliged to release them.
Even so, they will present the sternest of challenges to the team Jones has been forced to somewhat cobble together in the face of a long injury and suspension list. "We’ve lost 400 caps with the loss of the Vunipola brothers, Joe Launchbury and Courtney Lawes so that experience is hard to replace but we’ve still managed to name a very strong bench of finishers with Jamie George and Danny Care who are outstanding players and they will lead the final charge," Jones said.
On his selection of 29-year-old Wilson, who made his debut in Argentina in 2017, he added: "He is a very good defensive player, hard on the ball, gives everything to the team and certainly against the big South Africa forwards his chop tackling will be very important."
Owen Farrell runs with the ball during the England training session held at Browns Sport Club on November 1, 2018 in Vilamoura, Portugal.
Image credit: Eurosport
England, who have lost five of their last six full tests, take on New Zealand, Japan and Australia after Saturday's match, all at Twickenham.
England squad to play South Africa: 15 Elliot Daly (Wasps, 21 caps) 14 Jack Nowell (Exeter Chiefs, 26 caps) 13 Henry Slade (Exeter Chiefs, 13 caps) 12 Ben Te’o (Worcester Warriors, 13 caps) 11 Jonny May (Leicester Tigers, 37 caps) 10 Owen Farrell (Saracens, 61 caps) co-captain 9 Ben Youngs (Leicester Tigers, 77 caps)
1 Alec Hepburn (Exeter Chiefs, 2 caps) 2 Dylan Hartley (Northampton Saints, 93 caps) co-captain 3 Kyle Sinckler (Harlequins, 13 caps) 4 Maro Itoje (Saracens, 22 caps) 5 George Kruis (Saracens, 25 caps) 6 Brad Shields (Wasps, 2 caps) 7 Tom Curry (Sale Sharks, 4 caps) 8 Mark Wilson (Newcastle Falcons, 4 caps) Replacements 16 Jamie George (Saracens, 28 caps) 17 Ben Moon (Exeter Chiefs, uncapped) 18 Harry Williams (Exeter Chiefs, 11 caps) 19 Charlie Ewels (Bath Rugby, 6 caps) 20 Zach Mercer (Bath Rugby, uncapped) 21 Danny Care (Harlequins, 81 caps) 22 George Ford (Leicester Tigers, 47 caps) 23 Manu Tuilagi (Leicester Tigers, 26 caps)