The Panthers play in NCAA Division I Football Championship Subdivision (FCS) as a member of the Southwestern Athletic Conference (SWAC).

Before Hucles's arrival at Prairie View, the school played two games without a coach on record: a 1907 7–0 win against a team from Wylie, Texas[3] and a 1920 7–6 loss to Tuskegee University.

At the Panthers' peak under Nicks, Eddie Robinson was said to dread playing Prairie View.

Nicks was named the American Football Coaches Association’s recipient of the Trailblazer Award.

Prairie View is recognized as the first historically Black university to create and play in a post-season bowl game.

In May 1990, Prairie View shuttered all sports except track and field due to severe financial problems.

Due to this and other handicaps, new coach Ronald Beard found himself leading what he later described as an "intramural or club football" team at the I-AA level.

[5] On November 10, 2007, Prairie View clinched its first "official" winning season since 1976, and only their second since 1967, with a 30–27 victory over traditional power Jackson State University under then head coach Henry Frazier, III.

The next weekend would see the Panthers go undefeated in the SWAC by defeating Arkansas Pine Bluff and securing an 8–1 record; their only loss during the season was to New Mexico State.

Prairie View A&M hosted its first game on September 4, 2016, in front of a sold-out crowd, claiming victory in the Labor Day Classic over arch-rival Texas Southern, 29 to 25.

Prairie View finished its inaugural season in its new home stadium with three wins and one loss.

[12] Over 30 Prairie View alumni have played in the National Football League (NFL), including: [13]