Mutai set the course record the last time the NYC Marathon was held, in 2011. Sunday's race returned after last year's cancelation because of Superstorm Sandy.
Security was also heightened after the bombings at April's Boston Marathon.
On a windy morning, Mutai had an unofficial time of 2 hours, 8 minutes, 24 seconds, well off his mark of 2:05:06 set in nearly perfect conditions.
Jeptoo trailed Buzunesh Deba by nearly 3½ minutes at the halfway point. But she started making her move as the race entered Manhattan and passed Deba with just more than 2 miles to go.