In the men's race, Kenyan Geoffrey Kamworor held off countryman Wilson Kipsang to clock 2:10.53 and win by three seconds.
Flanagan, 36, finished in 2 hours, 26 minute, 53 seconds.
Marblehead native Shalane Flanagan won the New York City Marathon on Sunday, becoming the first American woman in 40 years to accomplish that feat.
Kenya's Mary Keitany, bidding for her fourth consecutive victory in the race, was 61 seconds back in second.
"This is the moment I have dreamed off since I was a little girl", Flanagan said after the race, tears streaming down her face.
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The 2017 event was held just five days after a deadly Manhattan truck attack that left eight people dead. Mamitu Daska, of Ethiopia, competing in the New York City Marathon for the first time, finished third with a time of 2:28:08. The race was described as a "very-well policed event, with many layers of security", said New York Police Department Chief Carlos Gomez.
As a student at the University of North Carolina, Flanagan also snared the school's first individual cross-country title in 2002, a feat she repeated in 2003.
After taking the lead in the 23rd mile, the 24-year-old 2015 NY runner-up had to contend with Kipsang, whose final push brought him ever so close to his countryman.
Flanagan placed sixth in the women's marathon in at the Rio Olympics a year ago, the top American finish.
Switzerland swept the professional wheelchair divisions. Keitany won the last three marathons and was second to Flanagan. Emmanuel Mutai from Kenya settled second in 2:03:13 followed by Ethiopian Abera Kuma in 2:05:56 and Kamworor 2:06:39.
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