Ndereba, the defending champion, finished in 2 hours, 25 minutes and 13 seconds, ahead of runner-up Elfenesh Alemu of Ehiopia. Ndereba is the first woman to win the race four times.
Negussie's time was 2:11.24. Second among the men was Wilson Onsare of Kenya.
Kenyan men had won 13 of the previous 14 Boston races.
More than 20,000 runners participated in the marathon -- the world's oldest -- which has been run since 1897.