Kimetto, who also won the Tokyo Marathon this year, ran the Chicago course in 2 hours, 3 minutes and 45 seconds, bettering Ethiopian Tsegaye Kebede's 2012 mark of 2:04:38.
All top four spots in the men's race were claimed by Kenyans -- second-place Emmanuel Mutai finished 7 seconds off the pace, followed by Sammy Kitwara and Micah Kogo.
Jeptoo, meanwhile, finished at 2:19:57, fully 51 seconds ahead of countrywoman Jemima Sumgong Jelegat on the women's side.
Jeptoo missed the Chicago title by just 1 second in last year's event when she finished just behind Ethiopia's Atsede Baysa.
A total of 39,115 runners crossed the finish line in Grant Park under ideal weather conditions.
Notable deaths of 2014 [PHOTOS]