Prop Joe Marler, who will not train until Friday after isolating with Covid-19, is named on the bench, as is uncapped hooker Nic Dolly.
Joe Marchant is on the wing with Manu Tuilagi returning to the midfield.
Flanker Courtney Lawes captains the side at Twickenham in the absence of the injured Owen Farrell.
England's last meeting with South Africa was the 2019 World Cup final in which the Springbok pack dominated to claim a 32-12 win.
Ex-British and Irish Lions prop Alex Corbisiero said during the week that England would face an "uphill battle" against the world champions without the experience of Jamie George.
So Rodd, receiving his second cap, and Blamire, gaining his fifth, face a tough Test at Twickenham, with prop Kyle Sinckler offering more international expertise in the front row.
George's injury offers 23-year-old Blamire the chance to continue a remarkable England journey that has seen him score six tries in four games, having only ever started three times previously for club Newcastle.
England's scrum will be propped up by six forwards on the bench, with number eights Alex Dombrandt and Sam Simmonds both named once again.
Head coach Eddie Jones said: "They said after the World Cup final, where they beat us fair and square, that they knew how to play us, they knew where our weaknesses were and they were implying that our forward pack was weak.
"Our forward pack's not weak and we'll have an opportunity on Saturday to show that.
"We are looking forward to taking them on in that physicality and we're also looking forward to try to expose the weaknesses in their game that they do have.
"There are opportunities to hurt them in other ways and we have to be brave enough to take those opportunities."