The overnight leader bogeyed the 15th hole to see his advantage at the top of the leaderboard cut to one stroke by South Africa's Charl Schwartzel but held his nerve the rest of the way to prevail by two strokes.
Kaymer finished on eight under par overall, with Schwartzel at six under and American Bill Haas alone in third, three strokes further back.
South Africa's Louis Oosthuizen began the final round just one stroke behind Kaymer, but a 74 on Sunday saw his challenge run out of steam and he ended in fourth place on two under, one stroke ahead of defending two-time champion Lee Westwood of England, who carded a 73.
Scotland's Paul Lawrie, the leader after the second round, went over par for the second day running as he managed 74 to finish in sixth place overall.
Kaymer famously sank the putt that ensured Europe retained the Ryder Cup earlier this year, but on a personal level this season has been a disappointment for the German.
And he admitted that as the opportunity to finally break his year-long victory drought edged closer, nerves began to tell.
"It was always tight," Kaymer told reporters.
"Charl played a great round of golf and I was telling (my caddie) that I need a win. I need a win in 2012."
Rainy conditions on the final day at Gary Player Country Club were in keeping with the previous three, meaning yet again that scores were kept in check by the weather.
No-one shot better than 69 all week, and that mark was again achieved by Kaymer on Sunday having also managed a three-under total over the second round.
The German began in positive fashion on Sunday, hitting a brilliant eagle on the second only to see his hard work erased with a double-bogey at three.
Birdies at nine, 10 and 11 took him clear of the pack again, although Schwartzel's birdie on the 14th trimmed the lead to one.
Kaymer hacked his way out of the rough to make an unlikely birdie on 14 and take his lead back out to two, but a bogey at the next meant the pressure stayed on.
Schwartzel's victory bid finally stuttered as he committed his first bogey of the day at the 17th, as Kaymer made par the rest of the way to close out an overdue victory.
"I'm very happy to finally win this year, that was the most important thing for me, because I was practising very hard," Kaymer added.
"I played very well the last few weeks and months, but it just did not happen for me on the golf course.
"I said to Craig, my caddy, we have to win one tournament every year and this is our last chance. Fortunately we could bring it home."
Collated final round scores & totals in the Sunshine Tour Nedbank Golf Challenge, Gary Player Country Club, Sun City (North West), South Africa
(Gbr & Irl unless stated, par 72):
280 Martin Kaymer (Ger) 72 69 70 69
282 Charl Schwartzel (Rsa) 72 71 70 69
285 Bill Haas (USA) 70 73 71 71
286 Louis Oosthuizen (Rsa) 71 72 69 74
287 Lee Westwood 71 73 70 73
289 Paul Lawrie 71 69 75 74
290 Francesco Molinari (Ita) 72 71 78 69, Carl Pettersson (Swe) 72 75 74 69
291 Peter Hanson (Swe) 72 73 73 73
293 Nicolas Colsaerts (Bel) 70 78 74 71
295 Justin Rose 73 79 69 74
297 Garth Mulroy (Rsa) 75 73 75 74