Kenyan Chepngetich smashed the women's record in Chicago last year, running 2:09:56 to become the first woman to break 2:10, and had hoped to improve on that time in London on April 27.
"I'm not in the right place mentally or physically to race my best in London, and I am therefore withdrawing," she said in a statement.
"I am very sad to miss the race, and I hope to be back next year."
Her compatriot Jepchirchir, a three-time major winner who won Olympic gold in Tokyo four years ago, has an ankle injury.
"I am focused on getting healthy again and hope to return to London again in the future when I’m fully fit," she said.
Vivian Cheruiyot of Kenya, the 2018 winner, is a late addition to the field.
This year's London Marathon is expected to break the world record for the most participants, with more than 56,000 people set to compete.