The big-serving Croatian overwhelmed a weary Nishikori in one hour, 54 minutes to clinch a ruthless victory and deny his 10th-seeded opponent's bid to become the first Asian man to win a grand slam. IN PICS: Marin Cilic wins US Open
With the win, 14th seed Cilic becomes the first Croatian to win one of the sport's four grand slam championships since his coach Goran Ivanisevic celebrated a Wimbledon victory in 2001.
"This is all hard work in these last several years and especially this last year," said Cilic. "My team has brought something special to me, especially Goran, we were working really hard but the most important thing he brought to me was enjoying tennis and always having fun."
"I enjoyed my best tennis over here and played the best ever in my life."
The final marked the first time since the 2005 Australian Open that at least one of tennis's big three of Novak Djokovic, Rafa Nadal and Roger Federer was not playing for the title.
The two players walked onto the Arthur Ashe Stadium court under overcast skies and much more forgiving conditions than the sweltering heat they faced through much of the fortnight.
While both men were playing in their first grand slam final it was Nishikori who displayed more jitters as Cilic quickly found his range and unloaded on his helpless opponent by blasting 17 aces to Nishikori's two.
Nishikori had his opportunities with nine break chances but could convert just one while Cilic was five of 11 and enjoyed a 38-19 edge in winners.
"It's a really tough loss but I'm really happy coming to my first final," said Nishikori, who appeared to run out of gas after beating three consecutive top-10 opponents and having to endure a pair of five-setters. "Sorry I couldn't get a trophy today but for sure next time.
"It was a really fun two weeks here. I hope I can be coming back next year," he said.
The big-serving Croatian overwhelmed a weary Nishikori in one hour, 54 minutes to clinch a ruthless victory and deny his 10th-seeded opponent's bid to become the first Asian man to win a grand slam.
IN PICS: Marin Cilic wins US Open