"It's a real character week for all of us now," said Johnson. "We can either pack it all up or come back and try to win the game. We have to bounce back and play our hearts out."
The Springboks, who had already beaten Wales and Scotland, made pre-match suggestions that they were too tired look laughable with a performance of classy opportunism in attack and dogged determination in defence.
Tries by Danie Rossouw, Ruan Pienaar, Adie Jacobs, Jaque Fourie and Bryan Habana and assured goalkicking by Pienaar after the break completed a hugely satisfying European tour with South Africa's sixth win in a row against England.
On a day that marked the fifth anniversary of England's 2003 World Cup triumph, the home side were given a stark reminder of how far they have fallen since that glorious night in Sydney and the heady days of seven successive wins over the Springboks.
"It was a brutal lesson," coach Martin Johnson told Sky Sports News. "We created a lot of opportunities but the execution was poor."
Springbok captain John Smit said: "We signed off in style. I asked a lot from the guys this week but they gave me more.
"I could feel it before the game, you know every guy is really on task and you get these wonderful days when everything comes together."
England got off to a flyer with a Danny Cipriani penalty in the first minute but it was very much a false dawn as within 20 minutes the Springboks had raced into a 17-3 lead, with all the points coming from English mistakes.
A penalty levelled it before Rossouw showed great strength to get the first try after England lost possession 10 metres from the South African line.
Ruan Pienaar helped himself to the second when he charged down a telegraphed Cipriani kick - the second time in three weeks the England flyhalf had given away a try in such fashion.
Lock Bakkies Botha then covered 40 metres at winger's pace to tackle Delon Armitage as the fullback seemed set to score.
Even with the visitors down to 14 men with prop Tendai Mtawarira in the sin-bin, England could make little impression and a penalty apiece made it 20-6 to the visitors at halftime.
England enjoyed some sustained pressure in the first 10 minutes of the second half but they were kept out by some determined defending and in the blink of an eye the Springboks extended their lead with a scything run by Jacobs.
England continued to enjoy the ball but made little impression, even when the visitors were again reduced to 14 with the loss of Conrad Jantjes.
Instead it was the "exhausted" Springboks who finished at the gallop with late tries for Fourie and Habana as the game ended up resembling last year's 38-0 World Cup pool stage humiliation more than the closely-fought final.
England's defeat, with the All Blacks to come next week, severely dents their chances of hanging on to their top-four place in the world rankings and could leave them out of the top seeds for the 2011 World Cup draw on December 1.
Tries: Danie Rossouw, Ruan Pienaar, Adi Jacobs, Jaque Fourie, Bryan Habana
Conversions: Pienaar (3), Francois Steyn.
Penalties: Pienaar (3).
Penalties: Danny Cipriani (2).
