NFL 2K3 is a single-player and multiplayer sports simulation game based on professional American football. The game aims to replicate the full NFL experience, letting players take control of any official team with updated 2002 season rosters, league realignments, and authentic stadiums. On the field, players control athletes across all positions, calling plays, executing strategies, and responding dynamically to changing situations. A television-style presentation frames the action, with an ESPN broadcast package that includes authentic score overlays, replays, and commentary, designed to resemble a live NFL telecast.

Gameplay emphasizes both individual player control and team strategy. A new play-calling intelligence system gives players additional flexibility when choosing offensive and defensive schemes, while the on-the-fly audible system allows plays to be adjusted at the line of scrimmage without breaking momentum. Animations were expanded to cover more realistic movements such as wrap tackles, sideline catches, and improved blocking. Game speed is influenced by timing and precision, requiring players to read the field and adapt as plays unfold.

The Franchise mode expands the game beyond the gridiron by placing the player in the role of coach and general manager as well as player. In this mode, teams must be managed over multiple seasons, balancing scouting, drafting, trades, and free agency with on-field performance. Player progression and team building are key factors, as poor management decisions can leave a franchise struggling while smart acquisitions may transform a team into a championship contender.

Additional modes include Exhibition for single games, Season for following a team through a full NFL schedule, and Practice to refine skills and test playbooks. Multiplayer is supported both locally and online, with online play making its debut in the series, enabling head-to-head competition across platforms.