The Kenyan’s time of 2.17:01 took 41 seconds off the mark set by Radcliffe on the same course in 2005, beating Tirunesh Dibaba into a distant second by almost a minute.
While Keitany was able to beat Radcliffe’s time for women-only starts, she fell short of the Brit’s extraordinary world record of 2.15:25, set with male pacemakers in the 2003 London Marathon.
She was on course to beat it several junctures of the race, having run the fastest split in history at 13 miles, at which point she had a predicted finish time of 2:13.48.
But she faded marginally in the final miles as she claimed her third London Marathon crown, coming after her wins in 2011 and 2012. Her compatriot, Jemima Sumgong, won in 2016 before she failed a doping test for EPO.
Dibaba stopped briefly after clutching her side with three miles remaining.
Britain’s Jo Pavey had hoped to be in the top two among her countrywomen in order to qualify for the World Championships, but dropped out after 16 miles.
Had she succeeded, the 43-year-old would have represented Britain at world level from 1500m to the marathon.
Alyson Dixon was the leading Brit, finishing 14th in 2.29:06.