It's Cilic's first grand slam title and Croatia's first since his coach Goran Ivanisevic beat Pat Rafter at Wimbledon wildcard in 2001.
Cilic beat Nishikori, the first Asian man ever to make a grand slam final, in straight sets 6-3, 6-3, 6-3, in under two hours.
Marin Cilic, winner of the US Tennis Open Photo: Photosport
This time last year, Cilic wasn't even playing while serving a four-month doping ban for testing positive to a banned substance.
The Court of Arbitration for Sport reduced the suspension from six months, but the scandal still rankles Cilic with the 25-year-old maintaining he tested positive for a banned stimulant contained in a supplement bought over the counter by one of his staff.
He was hoping his inspired run at Flushing Meadows helped restore his reputation.
It has certainly restored his ranking, with Cilic's added bonus for his grand slam breakthrough being a return to a career-high No.9 in the world for the first time in four years and a winner cheque of $NZ 3.6 million ($US3 million).
Cilic thanked Ivanisevic for helping turn his career around.
"The most important thing that he brings to me is the joy in tennis and I had lots of fun over here,"
Winner of the US Tennis Open Marin Cilic, who a year ago was serving a drug ban. Photo: PHOTOSPORT
The final was one of the most unexpected in grand slam history and marked many firsts.
Most notably, it was the first grand slam decider not featuring Federer, Rafael Nadal, Novak Djokovic or Andy Murray since Marat Safin beat Lleyton Hewitt at the 2005 Australian Open.
It was also the first featuring two grand slam final first-timers since Nadal downed Mariano Puerta to win his maiden major at Roland Garros in 2005.
Since then, the Big Four of Federer, Nadal, Djokovic and Murray had gobbled up 35 of the past 38 grand slam titles on offer.
Nishikori had taken out three of the top five seeds, including the top-ranked Djokovic in the semi-finals, and entered the final with a 5-2 head-to-head advantage over Cilic.
But unlike in his brave five-set comeback wins over fifth seed Milos Raonic and third-seeded Australian Open champion Stanislas Wawrinka, there was no fightback.
