The strike made early inroads and South Africa will believe it has a good chance of bowling out the opposition for a win on Sunday.
South Africa declared on 301 for seven wickets in their second innings at Supersport Park after their lower-order batsmen had blasted a tired England attack. England had to face six overs before the close, but Strauss was sent on his way for one run with the eighth ball of the innings.
The third ball Strauss faced, from Morne Morkel, found the outside edge of his bat and wicketkeeper Mark Boucher gleefully took the catch. Alastair Cook on four and nightwatchman James Anderson on six will resume on Sunday with the England total on 11-1.
South Africa's attack will relish bowling on the final day on a pitch with variable bounce. Batsmen Hashim Amla and A.B. de Villiers, who added 119 for the fifth wicket on Saturday to start turning the match, both remarked on the "up-and-down" bounce.
"Losing Andrew Strauss was a massive blow for England, and we'll have to work hard (on Sunday) but I think our bowlers are up to it," De Villiers said.
De Villiers hit 64 and Amla went on to record his seventh test century before falling to a ball which did not bounce above ankle height. Amla said the partnership had benefited from regular communication between him and Boucher.
"Everybody chipped in with the bat and the 50s down the order took the game away from England," Amla said.
Anderson said seeing off the new ball and concentrating throughout the day on Sunday would be crucial for England.
"It's going to be tricky, we have to get through the first hour and see off their big seamers and play the spinner well. We'll be looking to play the whole day and see where we are later in the afternoon," he added.
Morkel and Boucher had combined superbly as batsmen too, leading up to the second innings declaration. They smashed the England bowlers in an unbroken partnership of 35 in four overs for the eighth wicket, after number four batsman Amla had been dismissed for 100.
Amla was bowled by James Anderson. He batted for 315 minutes in an important innings for his side, and hit 10 fours. He went to three figures with a lovely flick through midwicket.
Boucher was at his pugnacious best, hitting nine fours and a six in his undefeated 63 off 72 balls Morkel slapped four fours in his 13-ball innings of 22 not out.
The best England bowler on the day was Anderson, who finished with 4-73. Broad claimed the vital wickets of Jacques Kallis and A.B. de Villiers, for figures of 2-58. He came in for punishment in the eighth-wicket stand, though, when he was hit for 29 runs in his last three overs.
In the second session the excellen, grafting fifth-wicket partnership of 119 in 136 minutes between Amla and De Villiers swung the momentum South Africa's way.
The home side added 102 runs in 29 overs in the middle session for the loss of only the wicket of De Villiers, well caught in the covers by Ian Bell off Broad for 64, with six fours and a six.
South Africa scored 418 runs in their first innings, to which England replied with 356.
Amla played a patient innings and gradually turned things around for his side with De Villiers as the England bowlers seemed to tire. At the end of the second session Amla was on 76 not out off 156 balls with eight fours.
Earlier England's bowlers struck three times in the first session to put South Africa under pressure on 80 for four wickets at lunch.
At that stage South Africa, 62 runs ahead on the first innings, was 142 runs ahead with five sessions left in the match.