Jeptoo followed up her victory at Boston by easily taking the women's raise, finishing in 2:19:57 after losing in a sprint a year ago. There was no one near Jeptoo as she turned into Grant Park, wearing a wide grin and waving to the crowd.
Jemima Sumgong Jelegat of Kenya (2:20:48) was second, followed by Maria Konovalova of Russia (2:22:46).
The winners each earned $100,000. Kimetto gets an additional $75,000 for the course record, while Jeptoo gets another $40,000 for finishing under 2:20:00.
On a sunny day with the forecast calling for temperatures to hit the high 50s when the top runners finished, conditions were close to ideal. But there was a different feel to this event in the wake of the Boston Marathon bombings, which killed three people and injured more than 260 others.
Police promised heightened security. More than a thousand uniformed and undercover officers and more bomb-sniffing dogs were expected to mix with the crowd along a course winding through 29 neighborhoods. Officers inside a command post were monitoring pictures coming in from helicopters and the city's 22,000 cameras, the most extensive surveillance system in the nation.
The Department of Homeland Security designated the marathon a "level two" event, a notch below massive gatherings such as the Super Bowl, which meant more federal agents with their own high-tech monitoring equipment.
Runners also saw changes.
They only used clear plastic bags issued by organizers to store their belongings near the finish line. They had to pick up their own packets, with race bibs and tracking devices, rather than friends or family.
Kimetto and Mutai started to surge ahead around the 19th mile, only to have fellow Kenyans Sammy Kitwara and Micah Kogo stayed with them. They faded after the group passed through Chinatown. Kimetto ultimately took control over the last few miles.
The world record of 2:03:23 was in sight, set by Wilson Kipsang of Kenya in Berlin two weeks ago. But ultimately, Kimetto settled for the course mark.
The 32-year-old Jeptoo had it easy down the stretch this time. Last year, she traded leads with Atsede Baysa of Ethiopia down the stretch and lost a step.
Six months later, Jeptoo won her second Boston Marathon, a victory that was overshadowed by tragedy.