Exeter flanker Johnson, 29, replaces the injured Tom Croft while Harlequins prop Joe Marler (pictured), 21, comes in for Alex Corbisiero.
"Tom and Joe have had great seasons at their clubs and have worked really hard to get this chance,” said head coach Stuart Lancaster. “Both are in great form and have really impressed in training.”
Ben Foden moves to the wing to replace the injured David Strettle, with Mike Brown coming in at full-back.
"Equally, Mike Brown has been outstanding for Harlequins,” continued Lancaster. “By moving Ben to the wing we retain his strike power and aerial skills. We can utilise not only Mike's attacking and defensive assets, but also call on his left-footed kicking game.
"We have made no secret of how tough this series will be but it is an opportunity we are looking forward to and I am confident that we can perform."
The other change to the starting XV sees Ben Youngs replace Lee Dickson at scrum-half.
Leicester fly-half Toby Flood returns to the replacements’ bench following groin and ankle injuries while Danny Care and James Haskell miss out altogether.
London Irish centre Jonathan Joseph could also be in line for a debut after he was named on the bench.
The tour will take in three Tests, with England also facing the Boks on Saturday June 16 in Johannesburg and the following Saturday in Port Elizabeth.
England team: 15-Mike Brown, 14-Chris Ashton, 13-Manu Tuilagi, 12-Brad Barritt, 11-Ben Foden, 10-Owen Farrell, 9-Ben Youngs, 8-Ben Morgan, 7-Chris Robshaw, 6-Tom Johnson, 5-Geoff Parling, 4-Mouritz Botha, 3-Dan Cole, 2-Dylan Hartley, 1-Joe Marler.
Replacements: 16 Lee Mears, 17 Paul Doran Jones, 18 Tom Palmer, 19 Phil Dowson, 20 Lee Dickson, 21 Toby Flood, 22-Jonathan Joseph.