Mahomes, 30, met with Lucy, a child undergoing treatment for acute lymphoblastic leukemia.
A video of this interaction was shared by the Chiefs on Instagram.
The star quarterback was filmed approaching Lucy and her family on the Arrowhead Stadium turf.
He then handed the young fan the game ball.
“What’s up Lucy, how you doing?” Mahomes said. “Appreciate y’all being out here today. I got a game ball for you.”
Lucy also handed Mahomes a miniature football for the quarterback to autograph.
Mahomes then signed a football for another young fan stood beside Lucy.
“Hope y’all are having a great night,” Mahomes then said as he signed the balls.
Quarterback Mahomes threw three touchdowns against the Commanders.
He also completed 25 of his 34 pass attempts on Monday as he threw for 299 yards.
The post was captioned with some words of support for the beaming young fan.
“Lucy is today’s Kingdom Champion!” it reads. “Lucy is progressing through treatment for ALL with inspiring resilience and loves gymnastics, volleyball, cheerleading, and softball.
“All of Chiefs Kingdom is rooting for you, Lucy!”
Fans have been quick to praise Mahomes for facilitating the once-in-a-lifetime opportunity.