Aiden Markram performed as well on his ODI debut as heh did on his Test debut, scoring 66 off 60 balls.
Quinton de Kock was once again successful at the top of the order with 73 off 68 balls.
Temba Bavuma was pushed up the order as a replacement for Hashim Amla and scored 48 off 47 balls.
Faf du Plessis was on course for a ninth ODI century when the South African captain was forced to retire hurt due to a lower back strain.
Kagiso Rabada struck three boundaries and one six in a quick-fire knock of 23 off 11 balls.
Rubel Hossain was slightly expensive but took the prized wicket of AB de Villiers.
Mehidy Hasan took 2 for 59 in ten overs.
Farhaan Behardien also struck 33 off 24 balls as South Africa mounted a massive total of 369 for 6.
The Bangladesh top order failed completely with South Africa reducing them to 20 for 3 and then 51 for 4.
Sabbir Rahman and Shakib al Hasan put on a partnership of 67 runs for the sixth wicket.
Shakib also scored a measured 63 off 82 balls.
Dane Paterson was the best bowler for South Africa, picking up three wickets.
But South Africa once again triumphed in the end by restricting Bangladesh to 169 and winning by 200 runs, sealing a 3-0 series sweep.