The tourists were 31 without loss at lunch after South Africa had declared 40 minutes before the interval on 270 for five, mindful of the inclement weather predicted for the final day on Monday.
Openers Chris Rogers (21) and David Warner (10) took Australia safely to lunch with few alarms on a pitch that still looks good for batting.
The highest successful run chase in test history was the 418 West Indies scored against Australia in Antigua in 2003.
South Africa will have to rely on their three seamers, Dale Steyn, Vernon Philander and Morne Morkel to do the majority of the work in the final innings with Wayne Parnell unlikely to feature due to a groin strain.
JP Duminy will bowl his part-time off-spin and Dean Elgar is another slow-bowling option.
Amla certainly had no trouble with the pitch, elegantly reaching his 21st test century to move joint third on South Africa's all-time list with Gary Kirsten, still behind Graeme Smith (27) and Jacques Kallis (45).
The 30-year-old brought up the milestone off 139 balls with 14 fours, most of them caressed through the covers.
He added 64 for the fifth wicket with debutant Quinton de Kock (34) before the latter was caught at slip by Michael Clarke off spinner Nathan Lyon.
Duminy scored an unbeaten 18 off as many balls as South Africa sought quick runs before the declaration.
Mitchell Johnson recorded the best figures for Australia with two for 51 in 15 overs and Peter Siddle took two for 89 in his 19 overs.
Australia won the first match of the three-test series by 281 runs in Pretoria.
(Editing by Ed Osmond)
