Ndereba pulled ahead just before the 21-mile marker near the crest of Heartbreak Hill and the pair ran together for several minutes before Ndereba sped away. Alemu finished 1:50 behind, second again.
Ndereba's four wins here tied her with Gerard Cote and Bill Rodgers. Only Clarence H. DeMar, who won seven times in the early 20th century, has more victories.
Catherine Ndereba makes her way along Boylston Street and toward the finish. She won the women's division in 2:25.13, 16 seconds ahead of Elfenesh Alemu.
(Mike Segar -- Reuters)
"Toward the finish I just felt great," Ndereba said. "I thank God for the history that I've made."
There were also repeat champions in the wheelchair races, with American Cheri Blauwet winning for the second straight year and South Africa's Ernst Van Dyk claiming his fifth straight win.
Negussie, who was fifth last year in his Boston debut, will have to wait a few years to make a similar claim on history.
Monday, he stayed with a huge chase pack through the first half of the race and eventually emerged in the hills with five Kenyans, including defending champion Timothy Cherigat and 2003 winner Robert Cheruiyot.
It was a perilous situation -- "I knew there were a lot of Kenyans, and I knew I had to break away someplace," Negussie said through an interpreter. In fact, the Ethiopian made more than one move, and by the 22nd mile none of the Kenyans had an answer.
Negussie, who grew up playing cricket and previously won marathons in Hofu, Japan (2001, 2002), and Xiamen, China (2003), said he had dreamed of a win in Boston "day and night" during his training.
"I think I did what I was dreaming of," he said.
Among Washington-area entrants, Centreville's Eric Post was 24th, Arlington's Michael Wardian 25th and Oakton High graduate Jacob Frey 26th. Wilson Komen, who trains in the District, was 16th.