Jeptoo showed her class by pulling away from the elite field and smiling and waving to the massive crowd as completed the 42.195 kms route through the Windy City in two hours 19 minutes 57 seconds.
Her compatriot Jemima Sumgong Jelegat came home a distant second in 2:20.57.
Jeptoo's relaxed win was in sharp contrast to the punishing battle she waged on the Chicago streets a year ago while suffering a one-second loss to Atsede Baysa.
Security was increased for the race, which attracted 40,000 runners, after the Boston marathon bombings in April which killed three people.
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