Cilic, the 14th-seeded 25-year-old, yesterday became the first Croatian man to win a major since Goran Ivanisevic, now his coach, at Wimbledon in 2001.
It also comes 12 months after he was forced to skip the tournament to serve out a controversial doping ban.
Cilic, playing in his 28th Grand Slam event, is the lowest-ranked champion since Pete Sampras, then 17th in the world, claimed the 2002 title in New York.
Monday's final was the first at a major not to feature either Djokovic, Federer or Rafael Nadal since the 2005 Australian Open -- so long ago that it was pre-Twitter.
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It was also a battle of contrasting styles between the 5ft 10in (1.78m), 150lbs (68kg) Nishikori and the bigger, heavier 6ft 6in (1.98m), 180lbs (82kg) Cilic who had knocked out five-time champion Roger Federer in the semi-finals.
Once he had saved a break point in the first game, Cilic was comfortably the dominant player breaking for 4-2 and claiming the opening set in 33 low-key minutes when Nishikori, on the defensive and pinned behind the baseline, patted a meek backhand into the net.