The win completes a clean sweep of victories against northern hemisphere sides in June following two defeats of Wales.
It is also the second heaviest defeat South Africa have inflicted on the Scots, bettered only by a 68-10 mauling in Edinburgh in 1997.
Willie le Roux and JP Pietersen were the other try scorers while debutant flyhalf Handre Pollard added five conversions and a penalty.
Replacement Marnitz Boshoff, also earning his first cap, added a further two-pointer.
Scotland replied with two first-half penalties from number 10 Duncan Weir.
South Africa lost none of their effectiveness despite missing 18 players through injury and seven more who returned to their English and French clubs this week.
"We are very happy with the game, just in the 15 minutes before halftime we got a bit loose and made some mistakes. But after halftime we pulled it together and started playing well again," captain Victor Matfield said in a TV interview.
Three tries in the opening 16 minutes gave the Springboks a 19-3 lead.
The first from Coetzee came three minutes in and before Scotland had even had a touch of the ball.
Weir landed a penalty but the home side's pressure was unrelenting and their second score was all about the pace of the back line as Pollard put Le Roux into a gap and he ran in his seventh try in 15 tests.
Mvovo's touchdown came from a clever grubber-kick behind the defence and the Sharks wing showed his pace to get to the loose ball first.
Weir added a second penalty when he opted to go for the posts from the halfway line rather than kick for the corner as South Africa led 19-6 at the interval.
After Pollard added another three-pointer Scotland's task became harder when lock Tim Swinson, just as he was about to be taken off, received a yellow card for holding back replacement scrumhalf Francois Hougaard.
From the resulting penalty South Africa set up a driving maul against a pack that was one man light and the inevitable try was scored by Coetzee.
The home side continued to make good use of their numerical advantage when a pass from Le Roux took out three Scots and found Pietersen on the right wing and he showed good strength to force his way over despite a covering tackle.
Henry Pyrgos' pass was then intercepted by Mvovo who was never going to be caught on a 60-metre run.
Pollard added the conversion from the touchline to make it 41-6 but there was still more misery in store for the visitors.
Coetzee broke through the defence and popped a pass for De Jager to romp home from 30 metres for his first international score - one that was quickly followed by his second as this time he crashed over from close range.
"We were disappointed with the way we started, we knew against the Springboks you have to start well," Scotland captain Grant Gilchrist said.
"We were a bit sluggish. There were aspects of the game where we fronted up well but too often we slipped off tackles and you can't do that against this opposition."
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