Bath Rugby Hooker, Lee Mears has been named on the bench for this Saturdays first test against South Africa in Durban, kick off 4pm BST.
Exeter Chiefs flanker Johnson and Harlequins prop Marler will win their first caps at Mr Price Kings Park in a team showing four personnel and one positional change from the starting line-up against Ireland in the final RBS 6 Nations outing.
Marler replaces Alex Corbisiero at loosehead, Johnson comes in for Tom Croft at blindside while there are also changes at scrum half, where Leicester Tiger Ben Youngs starts ahead of Lee Dickson and in the back three Northampton's Ben Foden moves to the left wing for David Strettle and to accommodate Harlequins' Mike Brown at full back.
England Head Coach Stuart Lancaster said: "Tom and Joe have had great seasons at their clubs and have worked really hard to get this chance, both are in great form and have really impressed in training.
"Equally, Mike Brown has been outstanding for Harlequins, By moving Ben Foden to the wing we retain his strike power and aerial skills and can utilise not only Mike's attacking and defensive assets we can also call on his left footed kicking game.
"It is competitive in lots of positions but particularly at scrum half. We are really pleased with Ben's form and he knows our systems well. Lee, if he gets his chance from the bench I am sure will make an impact and Danny will get his opportunity to press his case, as will the others, in the first midweek game on Wednesday.
"It's also great to see another young player get test match experience and Jonathan Joseph is delighted to get this opportunity in the match 22 and we are confident he is ready for the step up to this level..
"We have made no secret of how tough this series will be but it is an opportunity we do not fear and with the 22 we have selected, including an experienced bench, I am confident that we can perform."
Elsewhere, Owen Farrell starts at fly half and Scarlets No.8 Ben Morgan has sufficiently recovered from his hamstring strain to retain his place. England's most capped squad member Toby Flood, with 47, and British and Irish Lion Lee Mears provide experience on the bench. London Irish centre Jonathan Joseph, 21, could also make his Test debut as a replacement.
England Team to face South Africa
15. Mike Brown (Harlequins)
14. Chris Ashton (Northampton Saints)
13. Manusamoa Tuilagi (Leicester Tigers)
12. Brad Barritt (Saracens)
11. Ben Foden (Northampton Saints)
10. Owen Farrell (Saracens)
9. Ben Youngs (Leicester Tigers)
1. Joe Marler (Harlequins)
2. Dylan Hartley (Northampton Saints)
3. Dan Cole (Leicester Tigers)
4. Mouritz Botha (Saracens)
5. Geoff Parling (Leicester Tigers)
6. Tom Johnson (Exeter Chiefs)
7. Chris Robshaw (capt, Harlequins)
8. Ben Morgan (Scarlets)
17. Paul Doran Jones (Northampton Saints)
18. Tom Palmer (Stade Francais)
19. Phil Dowson (Northampton Saints)
20. Lee Dickson (Northampton Saints)
21. Toby Flood (Leicester Tigers)
22. Jonathan Joseph (London Irish)