Bangladesh were in trouble early in their reply and never recovered as they were bowled out for 141 in 18.3 overs.
All through the series, Bangladesh's batsman struggled against the home side's pace bowlers.
After thrashing Bangladesh in Test and the ODI series, the South African team continued their winning streak by defeating them once again in two-match T20 global series by 2-0.
In the final game of the tour, Miller hit five sixes in a row in the 19th over, and nine sixes and seven fours in all in his record-breaking innings.
The powerful left-hander struck 101 off just 36 balls - his century coming off 35 balls - to beat compatriot Richard Levi, who did it in 45 balls against New Zealand in Hamilton in 2012.
"It's a really special feeling", Miller told SuperSport. The first 50 came off 23 balls and the second 50 off just 12 balls as Miller went into overdrive mode.
The only players to hit six sixes in an over in an worldwide are South Africa's Herschelle Gibbs and India's Yuvraj Singh.
The Tigers also have more reasons to regret as Miller was dropped on zero off the bowling of Rubel Hossain.
Richard Levi took the T20 world and global cricket by storm as the SA batsman created history by scoring the fastest century in T20 internationals in just 45 balls where he smashed 13 sixes and remained unbeaten (Although now caught by Miller) 0n 117 in 2012.
Before Miller arrived South Africa was only 78-3.
Bangladesh suffered a clean-sweep against South Africa in all three versions of the game and skipper Shakib Al Hasan believes that it was majorly because the team could not do well in Tests.
Needing more than 11 an over from the start, Bangladesh didn't have the firepower to threaten the Proteas, a story that played out through most of the tour.