Kiley Lyall, from Chicago, was chosen for the shoot by the magazine's readers after sharing her story in a competition organised by the publication.
The 24-year-old has recently completed her second half marathon and says running helps her to de-stress.
Kiley began running at the age of eight and has barely stopped since.
When she ran her first half marathon she had a seizure at the 10 mile point but told her mum Kathleen that she wanted to complete the race.
Speaking to People magazine ahead of her daughter's cover debut, Kathleen said: "Kiley's been running for many years now, and people on the outside keep telling her how inspirational she is, and how she motivates them to want to run with all the struggles she goes through.
"One of my friends said this would be a really cool thing to enter because Kiley makes them want to run. But we never thought anything would come of it."
The proud mum added that running clearly has a beneficial effect on her daughter's health.
"Kiley started talking more and she started wanting to run more because it made her feel better," Kathleen said.
In an article inside Women's Running, the magazine's editor-in-chief Jessie Sebor says she was particularly inspired by Kiley's story when she looked through the competition entries.
"We’re so passionate about this cover and the opportunity to share Kiley’s story of determination. Our readers know that a love of running steams from many different places and sentiments," she says.
"We want to support all women on their running journey."
This isn't the first time Women's Running magazine has championed diversity.
In August, plus size model Erica Schenk graced the cover to prove that runners come "in all shapes and sizes".
At the time, Sebor said: "I think that every woman goes to the magazine rack sometimes and feels like she can't see herself in the cover images. We wanted our readers to feel like they could see themselves in our cover."