After a series of close finishes in the women's race - five consecutive years with 3 seconds or less separating the top two - Jeptoo had a relatively comfortable 33-second margin over Meseret Hailu of Ethiopia. Defending champion Sharon Cherop of Kenya was another 3 seconds back.
Shalane Flanagan, of nearby Marblehead, was fourth in the women's division in her attempt to earn the first American victory in Boston since 1985. Two-time winner Joan Benoit Samuelson, running on the 30th anniversary of her 1983 victory, finished in 2:50:29 to set a world record for her age group.
"The hardest part about Boston is the Bostonians want it just as bad as we do, which really tugs at our heart," said Flanagan, a three-time Olympian. "We all want it too. We want to be the next Joanie."
Kara Goucher, of Portland, Ore., was sixth for her third top 10 finish in Boston as many tries. The last American woman to win here was Lisa Larsen-Weidenbach in '85; Greg Meyer was the last U.S. man to win, in 1983.
"There's just more pure numbers of African runners," said Goucher, who noted that the field of five American women with personal bests under 2:30 was the strongest in years.
"That's a good team of American women. One day the opportunity is going to be there."
This year it was the men's race with the sprint to the finish.
Desisa, 23, was among a group of nine men - all from Kenya or Ethiopia - who broke away from the pack in the first half of the race. There were three remaining when they came out of Kenmore Square with a mile to go.
But Desisa quickly pulled away and widened his distance in the sprint to the tape. It's Desisa's second victory in as many marathons, having won in Dubai in January in 2:04:45.
Japan's Hiroyuki Yamamoto was the first winner of the day, cruising to victory in the men's wheelchair race by 39 seconds over nine-time champion Ernst Van Dyk of South Africa. Tatyana McFadden, a Russian orphan who attends the University of Illinois, won the women's race.
Race day got started with 26 seconds of silence in honor of the victims of the Sandy Hook Elementary School shooting. A little more than two hours later, the lead runners passed the Mile 26 marker, which was decorated with the Newtown, Conn., seal and dedicated to the memory of those killed there.