It was only the fourth career start at the 26.2-mile (42.16km) distance for Rupp, who was second in April's Boston Marathon and third in last year's Rio Olympics, and just the third marathon for Dibaba, a former world and Olympic 5,000 and 10,000m champion.
"It's just incredible," Rupp said. "You train so hard to have a race like this and to have it all come together, words just can't describe the feeling when I came across the line. It's just a great day."
Only one rival remained with Dibaba past the halfway mark as this year's London Marathon runner-up cruised to victory in 2:18:31, defeating Kenya's Brigid Kosgei by 1:51 with American Jordan Hasay third in 2:20:57.
"This is my third marathon and I'm very happy to have won here," Dibaba said. "I worked very hard for this."
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Dibaba and Rupp each took a $100,000 top prize at the 40th anniversary edition of the classic, which saw more than 40,000 runners compete on the streets of the US Midwestern metropolis.
Kenya's Dennis Kimetto, world record holder from his 2014 Berlin Marathon triumph in 2:02:57 and the 2013 Chicago champion, led at the halfway mark in 1:05:49 but began limping soon after and by 25km was off the pace for good.
The lead pack slowly dwindled over the next 10km, leaving only Rupp, Kirui and Ethiopia's Sisay Lemma after 22 miles.
Rupp, who took 2012 Olympic silver at 10,000m, made his charge with three miles remaining and no one had a response.
"I just tried to relax and when I make the move be decisive. It feels tremendous. I feel so great I was able to pull it out."
- Dibaba dominates -
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Dibaba vowed to challenge the women's course record of 2:17:18 set by British world record holder Paula Radcliffe in 2002 and was on that pace in the early going.
Dibaba led after 5km in 16:08, 19 seconds under Radcliffe's course record pace, and had trimmed the field in the lead pack to only five.
Dibaba led at the halfway mark at 1:08:48, well off Radcliffe's record pace, but made another charge that left only Kosgei on her heels. The Kenyan fell back with 10km remaining, leaving Dibaba alone to the end.
Dibaba, 32, is a two-time 5,000m world champion and three-time 10,000m world champion.
She won 5,000 and 10,000 gold at the 2008 Beijing Olympics and defended the longer crown four years later in London. Last year in Rio, Dibaba was third in the 10,000.