Kirui, who has battled a litany of injuries since winning silver at the 2012 London Olympics, clocked 2hrs 11min 23sec with Chumba second in 2:11:26 and Gideon Kipketer third in 2:12:20.
"I was putting in my prayers and efforts in winning today," said 34-year-old Kirui. "I had a very strong mind, this time I knew it was a matter of life and death. The course favoured me and I was lucky that the weather was not so humid."
While Chumba was unable to repeat his 2015 triumph, Kenya's Florence Kiplagat won her second straight Chicago crown, powering to a dominant victory in 2:21:32, almost two minutes ahead of runner-up Edna Kiplagat's 2:23:28.
With two kilometres remaining Chumba and Kirui had separated themselves and were jockeying for the lead before Kirui, running in Chicago for the first time, made a decisive move.
"It’s wonderful, amazing," said Kirui, who was embraced by training partner Kiplagat after the women's winner crossed the finish line.
Her dominant display ensured there was no finish-line drama in the women's race, in which a tight-knit leading group set a more methodical pace through the first two-thirds of the race than the top men managed.