Radcliffe had only recently returned to full fitness
Paula Radcliffe failed to defend her New York Marathon title on Sunday.
Britain's world record holder finished fourth and clutched the back of her left leg in pain as she came home.
The women's elite race was won by two-time Olympic 10,000m champion Derartu Tulu of Ethiopia, who saw off Russia's Ludmila Petrova in the final kilometre.
In the men's elite race, Meb Keflezighi become the first American to win since 1982. The Eritrean-born runner became a US citizen in 1998.
Radcliffe, 35, was running her first marathon since winning in New York 12 months ago. She was sidelined for six months earlier this year after bunion surgery.
The Briton missed the world championship marathon in Berlin in August and then sat out the World Half-Marathon Championships in Birmingham last month because of tonsillitis.
After Sunday's race, she revealed tendinitis behind her knee had started to take its toll before the halfway stage.
"I knew I was fit coming in, it felt great, then at 11 miles it just went," Radcliffe said.
"For the last miles I was just thinking 'just hang in there' as long as I could. Just try to stay with them."
Radcliffe said she had had a cortisone injection last week to help ease the problem.
"I'm just very disappointed," she added. "The really frustrating thing is I don't even feel tired now but my legs just couldn't go any quicker."
In windy conditions, the pre-race favourite led from the gun, but the relatively slow pace meant she had been unable to shake off her rivals.
Keflezighi's win completed his comeback from a hip stress fracture
And, at 23 miles, she was dropped from the leading quartet as Petrova took off followed by Tulu and Daunay.
Tulu, 37, first shook off Daunay and then the dogged Petrova at the 26-mile mark, beating her by eight seconds.
Petrova, 41, runner-up in New York for the second straight year, was followed home by Christelle Daunay of France.
Daunay held off a late push by Radcliffe to come home in 2:29:16, with the Briton clocking 2:29:27. Tulu last won a major marathon in London in 2001.
Keflezighi, 34, the 2004 Olympic silver medallist, was second in New York in 2004 and third in 2005.
Sunday's victory completed his comeback from a stress fracture in his hip diagnosed after a disappointing US trials in the Big Apple race two years ago.
He won in a two hours, nine minutes and 15 seconds ahead of four-time Boston Marathon champion Robert Cheruiyot of Kenya. Jaouad Gharib of Morocco finished third.
Keflezighi said: "The USA gave me all the opportunities there is in education. To be able to represent the USA is a big thing for me."
The last American man to win before Keflezighi was Alberto Salazar, who won three consecutive New York races from 1980-82.