The Frenchman was looking to make it third time lucky after back-to-back final defeats in Kuala Lumpur in 2012 and 2013.
World number 28 Benneteau lost out to Juan Monaco two years ago before coming off second best against Joao Sousa 12 months ago, despite winning the opening set.
But Benneteau was unable to break the hoodoo on Sunday, succumbing to the US Open runner-up as Nishikori claimed his third ATP title of 2014.
Fourth seed Benneteau made a strong start and broke his opponent early in the first set.
Serving at 5-4 up, Benneteau allowed Nishikori to hit back before the Japanese top seed went on to clinch the tie-break having won 81 per cent of points on his first serve.
Nishikori saved two break points in game four of the second set and the world number eight broke Benneteau to love in the seventh game to take a significant step towards victory.
After consolidating with consummate ease in the next game, Nishikori closed out the win in game 10 to ensure Benneteau's Malaysia Open anguish continued.