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  Malan targeted South Africa's seamers, striking 12 fours and two sixes in a 44-ball knock as England posted 181-8.
  Chris Jordan took 3-31 and Tom Curran - in only his second game - 2-22 to restrict the Proteas in their chase.
  AB de Villiers made 39 and Mangaliso Mosehle 36 off 22 balls but South Africa could manage only 162-7.
  England, returning to the venue of their Champions Trophy semi-final defeat by Pakistan, put in a professional performance to wrap up the series.
  Middlesex left-hander Malan, 29, made the highest score by an England player on T20 debut, beating Paul Collingwood's 46 in England's maiden match in this format in 2005.
  England, whose next white-ball series is not until September against West Indies, begin a four-Test series against South Africa on 6 July.
  It was a polished performance from England's bowlers, using the short ball to discomfort South Africa, and they were backed up by some strong fielding.
  Hampshire leg-spinner Mason Crane, who played in the opening T20 at Southampton, was put under pressure as de Villiers struck him for consecutive sixes.
  However, the 20-year-old showed admirable confidence as he continued to toss the ball up and was rewarded when he drew an error out of the tourists' skipper, who slapped the ball to Alex Hales on the deep square leg boundary.
  Crane rounded off his spell with a superb over, conceding only two runs as England turned the screw.
  The Proteas were lacklustre. Of the top six, only De Villiers and opener JJ Smuts (29) reached double figures and it took some big hitting from wicketkeeper Mosehle to push their total up.
  England's seamers were excellent, with Curran in particular showing a maturity at the end of the innings as he bowled full and straight.
  The result means the visitors have won only two of their six limited-overs matches on this tour.
  England captain Eoin Morgan chose to rest himself for the match, a decision that initially drew criticism given this was a must-win game for England, but big-hitting Malan adapted quickly to international cricket.
  Arriving at the crease after Jason Roy fell for eight, Malan left his first delivery but pulled the second ferociously into the stands for six.
  On a pitch tinged with green, he took on the short ball against the seamers.
  He did not let up against a change of pace, nonchalantly flicking leg-spinner Imran Tahir over his shoulder to bring up his half-century from 31 deliveries.
  Malan and Hales, who was struggling to run after edging the ball on to his knee, put on 105 in 10.3 overs.
  When Malan finally fell, caught at long-on off Tahir, stand-in captain Jos Buttler struck two flat sixes to push England above 180.
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  The manner in which England went about such a calm and assured victory will be more heartening giving the changes they made to their side.
  As well as Morgan being rested, England gave Crane another opportunity, as well as Curran.
  For South Africa, it was a disappointing return, given how strong they were in the closing stages at Taunton.
  They were sloppy in the field to begin with. Andile Phehlukwayo's drop to reprieve Hales on 13 was so surprising the batsman had turned to walk back to the pavilion.
  South Africa will take some comfort in the performance of right-armer Paterson, who was twice on a hat-trick in the final overs thanks to his mixture of yorkers and slower balls.
  However, it was England who controlled the majority of the game.
  England stand-in captain Jos Buttler: "Dawid Malan was fantastic on debut. It is not easy to come in and show that much composure under pressure. On debut it was a fantastic effort.
  "Mason Crane, for a 20-year-old, has got great character. He was bowling at one of the best players that have ever played the game on a ground with a short boundary.
  "It was very tough on him but all credit for having the bravery and guts to keep going and get the wicket. I am sure he will remember it for a long time.
  "We have found some really great players. You find out a lot about players - international cricket is different and those guys have stepped up. Tom Curran was brilliant for his two games.
  "Taunton is not an easy place to make your debut and he took three wickets and two today. He looks a real find."
  South Africa captain AB de Villiers: "We were outplayed in both of these series. Well done to England and Eoin Morgan in the majority of the games, and Jos Buttler today, for leading them.
  "England put in an all-round better performance today. We were not far off but it was disappointing.
  "England do have some really good youngsters. They have good depth and all round are a really good team.
  "They seem to be going through a good patch and have a lot of talent. They have a bright five to 10 years ahead of them."
  On Mason Crane: "I was always going to go after him. Well done to him for sticking to his guns."
  Dawid Malan, who was named man of the match: "It is a fantastic experience to play for your country and to contribute in a win like that on debut is fantastic.
  "I thought this day might never come. I had a chat with Adam Voges, who played later for Australia.
  "I asked what he did and how he kept motivated when you keep getting overlooked for younger and younger players. He gave me some advice and fortunately I had a good Lions series and got picked when players were rested."
target: Dawid Malan hit an aggressive 78 on debut to help England beat South Africa by 19 runs and complete a Twenty20 series victory in Cardiff.