Jeptoo overtook front-running Ethiopian Buzunesh Deba with about two miles to go to win going away in two hours, 25 minutes and seven seconds and claim a huge payday.
London Marathon winner Jeptoo trailed last year's New York runner-up Deba, who lives and trains in the Big Apple, by nearly four minutes before shifting into catch-up mode from the 16-mile mark to reel in her rival.
The win brought Jeptoo a World Marathon Majors bonus of $500,000 in addition to the New York prize of $100,000.
Deba finished second, 49 seconds back, in a race run under tight security in the aftermath of the Boston Marathon bombings with twice NYC winner Jelena Prokopcuka of Latvia third.
Mutai had to wait a year before defending his title after the 2012 race was cancelled due to damage inflicted by Superstorm Sandy, but the 2011 Boston winner showed he had not lost his edge as he hit the Central Park finish 52 seconds ahead of Tsegaye Kebede of Ethiopia.
"Today was a very tough race," said 32-year-old Mutai, who finished in 2:08:24. "To win a race for the first time is easy. To defend your title is not easy."
In third place was Lusapho April of South Africa in 2:09:45.
Kebede had reason to smile, however, as his second-place finish allowed him to clinch the men's $500,000 World Marathon Majors bonus prize.
Tatyana McFadden completed a sweep of major marathon women's wheelchair titles, winning her second New York City race in addition to this year's victories in Chicago, Boston and London.
Marcel Hug of Switzerland won the men's wheelchair race.
(Editing by Ed Osmond)
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