NFL Blitz for Game Boy Color is an adaptation of the football game of the same name released on other platforms. While it features the same style of arcade gameplay with loose rules, it has slightly different features and presents everything in platform-appropriate two-dimensional graphics.

Among the deviations from standard NFL football are 30-yard-downs, seven-man teams, legal pass interference, the clock stopping after every play, and the absence of referees. Play modes include exhibition games and a full season with progress saved via password. Quarter length can be set between one and six minutes. Players can select from the 30 teams of the 1998 NFL season. Differences from other versions include different featured star players and the season not following any real-life schedule.

Gameplay is seen from an isometric perspective. The playbook (same as in other versions) includes 18 offensive and 9 defensive plays, which are flippable. On offense, players can engage a turbo to run faster, and launch evasive moves like spins and hurdles while on defense, the controlled player is freely switchable and is capable of diving and tackling.

The Game Boy Printer is supported for printing out stats and passwords.