JOIN USSouth Africa were 191 for three at tea, an overall lead of 160. Amla was on 69 and De Villiers 54. Their fourth wicket stand was worth 101.
The pair had to survive some hostile bowling from 18-year-old fast bowler Pat Cummins, who struck twice as South Africa lost three wickets before lunch.
Cummins bowled immediately after lunch and had a confident shout for leg before wicket against Amla turned down by umpire Billy Bowden. The Australians asked for a review and Bowden's decision was upheld when replays showed the ball would have hit the leg bail - in the umpire's discretionary area.
De Villiers also had a close escape against Cummins when he edged the ball down the legside dangerously close to wicketkeeper Brad Haddin.
Cummins dismissed Jacques Rudolph for 24 and Jacques Kallis for two as the advantage in the morning swung to Australia, who need a win to level the series.
South Africa also lost captain Graeme Smith, who made 36 before cutting off-spinner Nathan Lyon to backward point.
Starting the day 30 runs behind Australia's first innings total, South Africa quickly wiped out the deficit, with Rudolph looking in outstanding form as he made 24 off 23 balls with five fours. But with the total on 40 Rudolph tried to pull a short ball from Cummins which rose sharply into his body and the ball looped off the splice of his bat to wicketkeeper Brad Haddin.
Smith was out tamely to Lyon and the scoring rate slowed as Amla and Kallis concentrated on defence.
But Cummins came back into the attack and produced a good delivery which Kallis edged to Australian captain Michael Clarke at first slip.