England head coach Eddie Jones says young players like Bevan Rodd and Jamie Blamire "can change the course of rugby history" against South Africa.
Prop Rodd, 21, starts on his second England appearance, with Joe Marler on the bench after isolating with Covid.
Blamire, 23, takes injured hooker Jamie George's place and both he and Rodd face a famously strong Springbok pack.
Jones told BBC Sport Saturday's challenge at Twickenham is "a great opportunity for these young guys".
"They can change the course of rugby history," he added.
South Africa have won 26 of the 43 Tests played between the two sides, with the most recent victory coming in the 2019 World Cup final.
Jones continued: "Sixty-five percent of the Tests between South Africa and England have been won by South Africa so we can change that course of history. These young guys have got it in them."
'No doubt Rodd and Blamire can do the job'
With captain Owen Farrell also injured and senior faces like Mako Vunipola and George Ford overlooked this autumn as new players are tested for the 2023 World Cup, Jones estimates Saturday's squad has three-quarters of the caps of a normal England line-up.
Nevertheless, the England coach insists Rodd and Blamire, who will win his fifth international cap on Saturday, "can do the job" against the world champions.
"There's no doubt about it," added Jones, whose side have beaten Tonga and Australia this autumn.
"For young front rowers, these are the sorts of games you want at the start of your career.
"You're up against it. The opposition fancy themselves a bit. You can prove yourself to be an outstanding player and they will."
When asked if he had considered bringing the experienced Mako Vunipola back into camp after Marler and Ellis Genge contracted coronavirus, Jones said: "No, not really.
"We've made a decision that those guys need to play more club rugby and find that consistency in their performance.
"We're quite happy to play Bevan Rodd. We think he's the right man for the job."
Marler's isolation means his first training session with the rest of the England team will be on Friday, but Jones said the loose-head "will be in good shape", adding: "We're happy to put him on when we need him."
South Africa's dominance up front was a big factor in England's World Cup final loss, but Jones says England will not shy away from the set-piece in their gameplan despite a lack of experience in the front row.
"You've got to take them on there," he explained.
"They don't go away in the set-piece so you've got to take them on and you've got to fight to the death. I know our forward pack is not weak."
'Hopefully they check the laundry baskets for Erasmus'
South Africa will be without director of rugby Rassie Erasmus at Twickenham after he was banned from Springboks matchdays for a year by World Rugby.
Erasmus will appeal the punishment, which came as a result of an hour-long video criticising the refereeing of South Africa's first-Test defeat by the British and Irish Lions in July.
Jones suggested Erasmus might still find a way into Twickenham, joking that he could follow the example of Jose Mourinho, who hid in a laundry basket to attend Chelsea's Champions League quarter-final from which he was banned in 2005.
"Hopefully they're going to check the laundry baskets - Rassie might be hiding in there," Jones said.
"They're very good at galvanising the emotion of the situation and I'm sure they'll use the situation to their advantage.
"They've got a strong sense of unity, they've got a strong sense of country pride and that carries them a long way."