The Croatian, 28, triumphed 6-1, 7-6 (7/5) on Sunday over his higher-ranked opponent in a repeat of the 2014 US Open final, where he also defeated Asia's best player.
Cilic, ranked 12th in the world, currently holds the last of the qualifying spots for the World Tour Finals in London but will face a battle this week at Paris Bercy in the final event of the regular season to keep the place.
Eight players will take part in the prestigious London showpiece on November 13th-20th.
“Paris will be deciding everything, I want to finish the regular season in a good way and hope to refresh myself in the next couple of days to be ready again,” Cilic said, after earning his 16th career title from 27 finals.
“I now have the first 500 series title in my career. I'm adding it to all my other trophies. It shows me that I'm in a good way, I'm playing very well.
“I had pressure all week fighting to qualify for London. But it was a great week for me, I played some good tennis.
“I feel great, it was a tough week, there was a lot at stake. I came up with some great tennis despite the pressure.”
His Basel success was the second title of the season for Cilic after winning his first Masters 1000 title in August in Cincinnati, beating Andy Murray.
“Today I started the match with good energy and motivation, a few balls can decide a lot. I was quite focused in the critical moments,” Cilic said. “My game was really high and level was quite big today.”
World number five Nishikori, who already knows that he is on his way to London for the third straight year, refused to make excuses.
“I didn't feel I was in there all the time. If I could have won the second set, maybe something would have changed,” he said.
“In the end, I didn't feel comfortable and didn't feel the balls well today.
“It was a combination of his good tennis and the fact that I was not at 100 percent. In the second set it was close, I had a couple of set points but couldn't convert.”
Cilic ended with a modest six aces, producing his last one at just the right moment to earn a pair of match points.
He put a forehand long on the first but claimed the match — and the title — when Nishikori hit a double fault on the second.
The Japanese, who will also be in Paris, was playing his fifth final of the season — but can boast only the Memphis title from February.
On Friday, top seed and US Open champion Stan Wawrinka slumped to a shock 6-2, 5-7, 6-1 defeat to German qualifier Mischa Zverev in the quarterfinals.