Thrust in to open the batting in his first Test in almost a decade, Maddinson lasted 33 balls in Durban before his difficult innings ended when he chopped on from Marco Jansen.
With Travis Head also falling early on Friday, Marnus Labuschagne was then lbw to Wiaan Mulder on the last ball before lunch for 37 after a 60-run stand with Steve Smith (25no).
Labuschagne had looked in reasonably good touch until that point, but was unable to overturn the lbw call, with ball tracking showing "umpire's call" on impact.
Smith had earlier made a point to take after South Africa spinner Keshav Maharaj in his first over, lifting the left-armer back down the ground for two sixes.
But the talking point of the morning was Maddinson, who was a shock call-up to Australia's Test squad last week when Josh Inglis fractured his finger.
The 34-year-old only underwent chemotherapy to beat testicular cancer last year, with his last of three Tests coming against Pakistan on Boxing Day in 2016.
As much as it was a feel-good story, critics also pointed to the fact Maddinson had not played a first-class fixture for more than 18 months.
The most vocal criticism came from former Test opener Matthew Hayden, prompting Head to hit out at what he saw as a habit of negative comments from former players.
A bigger surprise awaited when Maddinson was then selected in the XI on Friday, and then chosen to open the batting, with Matt Renshaw moving down to No.5.
In doing so, it gave Head his third opening partner in three Tests, following Jake Weatherald's axing after Australia's loss to Bangladesh in Darwin.
Australia have now used eight specialist opening pairings since David Warner retired in January 2024, not counting nightwatchmen or injury-enforced in-game changes.
Australia's coaching staff had talked up Maddinson's flexibility and ability to play spin this week, but ultimately the call did not receive the pay-off in the first innings.
The left-hander was lucky to survive his 15th ball when South Africa opted not to review an lbw appeal from Mulder that would have been out on ball tracking.
When dismissed, it made for Australia's second-longest duck in Test cricket when balls have been recorded, behind Mike Whitney's 42-ball effort against England at Old Trafford in 1981.
Maddinson's was also the third-longest on record of any opener worldwide in Test history.
At the other end, Head clipped two boundaries off his pads before edging one down legside off Mulder on nine.
