The world number seven - runner-up at this year's US Open - held off a strong challenge from the Canadian to win the ATP 500 hard-court event for the second time in three years on home soil.
Nishikori had also beaten Raonic in the 2012 showpiece and defeat in Tokyo completed an unwanted treble for the world number eight, who has now lost each of the past three finals after losing out to Juan Martin Del Potro 12 months ago.
For Nishikori, victory clinched his second successive ATP Tour crown after he saw off Julien Benneteau in the Malaysia Open last week.
The win also moves the Japanese a step closer to qualification for the ATP World Tour Finals in London next month as he aims to become the first Asian player to compete in the season-ending tournament.
"It's been incredible. The first time that I won two weeks in a row," said Nishikori.
"After the US Open, it was hard to maintain that motivation. The first time in the final of a grand slam, it was my dream, and tough to change mentally, to stay strong and focussed all the time.
"Especially this week I wasn't feeling 100 per cent, but to win the tournament, it's getting a lot of credit."
The opening set was a closely-fought affair, with neither player forcing a break point as the duo dominated their respective service games.
Nishikori took the tie-break at the first available opportunity, but Raonic hit back in the second after sealing the first break of serve in game seven.
After forcing the final into a decider, the Canadian managed to save three break points in his opening service game as Nishikori cranked up the pressure.
Raonic was unable to hold out in game 10, however, as Nishikori broke for the first time in the match at a crucial stage, closing out the win and claiming almost $300,000 in prize money.