Jack Hoffman, 13, donned the No. 75 jersey when he took the field on Monday for the West Holt Junior-Senior School Huskies. The team won 38-0.
Jack's family said the eighth-grade student wanted to play football even while continuing to undergo treatment in his ongoing cancer fight. His doctors also gave him the OK to finally play.
"This isn't something that we're shoving down his throat," said Andy Hoffman, Jack's father, according to the Associated Press Thursday. "Whether you have a brain tumor or not, you should make the most out of today. That's what Jack's doing."
Jack , of Atkinson, Nebraska, was first diagnosed with cancer at the age of 5 after he suffered a seizure in 2011.
A Cornhusker fan, Jack attended his first game on his fifth birthday. Before his second brain surgery in September 2011, Jack's family reached out to the University of Nebraska and arranged for him to meet Burkhead and tour the stadium.
In April 2013, Jack, then 7, sported a specially sized Nebraska Cornhusker No. 22 uniform -- the number of his favorite player, Rex Burkhead -- and ran with the entire team for 69 yards to score the game's final touchdown.
During that meeting, Jack and Burkhead formed a friendship.
In August 2014, when Jack was 8 years old, his family shared that his tumor was growing again after having been in remission.
Jack has spent the last few years fighting brain cancer and raising awareness about pediatric brain cancer along with his family as part of the Team Jack Foundation. His parents started the foundation in his honor, and it aims to raise money for pediatric brain cancer research. They have now raised more than $8 million.
Burkhead now plays for the New England Patriots and is also a supporter of the foundation.
In July 2013, Jack earned an ESPY award for "Best Moment" because of his touchdown video. He also had a chance to meet former President Barack Obama in the Oval Office in April 2013.
ABC News' Gillian Mohney and Katie Kindelan contributed to the reporting in this story.