The second-seeded Cilic broke his opponent in the fifth game to grab the opening set, but Nishikori turned the match on its head with an inspired fightback to send the two-time defending champion packing.
In other matches, Robert Kendrick of the United States, Bjorn Phau of Germany, and Stephane Robert of France, recorded straight-set victories to make the second round.
Story continues below ↓advertisement | your ad here"I'm a little bit disappointed the way I have started the year. I wouldn't say I played too bad ... I didn't have luck at crucial moments, the key points he played better than me," Cilic said.
The 98th-ranked Nishikori, who defeated Cilic in a tough five-setter in the second round of the U.S. Open last year, outpaced the Croatian in a dramatic second set in which he saved three break points in the 11th game.
"The first two sets were very close. (My) losing the second set, he took the momentum from me," Cilic said. "The momentum he got, the way he played after that, I could not come back."
The 21-year-old Nishikori won the tiebreak without dropping a point and then broke Cilic in the first game of the third set to take an early grip on the decider before serving out for the match after breaking again in the seventh game.
"I was nervous, first match for me ... new coach (Brad Gilbert), new trainer. (But) it was a good match today," Nishikori said of the opening set.
The Florida-based Japanese attributed his fightback to changes he has made to his game.
"Not to miss easy balls, not doing crazy stuff ... (to play) more percentage tennis," he said. "In the second set I tried to make most of my first serves ... I was making him move."
Meanwhile, sixth-seeded Serbian Janko Tipsarevic kickstarted the new season with a 6-3, 6-4 victory over Eduardo Schwank of Argentina and in another late match, Ivan Dodig of Croatia scored a 6-2, 6-2 win over Brazilian Marcos Daniel.
No. 6-ranked Tomas Berdych heads the field and the Czech will open the new season on Tuesday with a first round match against Frederico Gil of Portugal.
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