She held off competition from the likes of compatriot Brigid Kosgei, who was bidding to win the event for a third consecutive year but could only manage a fourth-place finish.
Jepkosgei, who won the New York Marathon in 2019, smashed her own personal best to become the seventh-fastest woman in history over the distance.
She finished ahead of Ethiopia’s Degitu Azimeraw and Ashete Bekere, who finished second and third respectively.
In the men’s elite race, Sisay Lemma of Ethiopia was a comfortable winner, finishing in a time of two hours, four minutes and one second.
He raced 27 seconds ahead of Kenya’s Vincent Kipchuma in second, with Mosinet Geremew coming in third.
Meanwhile, Switzerland’s Marcel Hug and Manuela Schar completed a double for their country in the elite wheelchair events.
Both set new course records, with Hug winning the men’s race in one hour, 26 minutes and 27 seconds.
Schar then set a new course record in the women’s race, finishing in a time of one hour, 39 minutes and 52 seconds.
In near-perfect conditions, about 36,000 participants tackled the traditional course from Greenwich to Westminster for the first time in more than two years.
Last year’s marathon was held on a modified course — 19.6 laps of St James’s Park in the shadow of Buckingham Palace — and only staged the elite races due to the pandemic.