Labuschagne appeared in superb touch before his departure, forcing boundaries off both back and front foot and collecting regular singles. But when he attempted to punch a cover drive off spinner Keshav Maharaj, enough turn and bounce skewed the ball to Temba Bavuma at cover, a soft end to another promising innings.
Daniel Brettig, reporting from Durban, said the twin dismissals would only reinforce the perception that Labuschagne's struggles are mental. "His struggles to make big scores appear to be in his head," Brettig wrote, noting the batsman had been timing the ball beautifully up to the error.
Matt Renshaw, who had earlier slapped a pair of reverse sweeps to the boundary, continued his fluent start on 20 off 19, with Alex Carey joining him after Steve Smith's departure. Australia's lead was growing at 3-157 as the hosts searched for quick wickets.
The tourists entered day four in the box seat after Smith and Pat Cummins' efforts on day three, which included three brilliant catches from Smith in the field.
South Africa's spinners have been Australia's main source of trouble, with Maharaj's turn and bounce providing the breakthrough, but the home side will need early wickets on day five to keep the match alive.