The game features a franchise mode with a SportsCenter feature hosted by Chris Berman. He outlines the games of the current week with his co-host Trey Wingo who talks about the latest injuries and free agent deals and trades during the season. Mel Kiper Jr. hosts the draft portion of the segment while Suzy Kolber reports from the sidelines. There is also weekly preparation for the coming week which allows the player to make decisions on training and preparation. The player can also create their own team deciding the team logos (over 10 are available), team name, the team's city, the team's stadium look and build, jerseys and how good the team is. It also has a feature called first-person football, which gives the player the experience on the field looking from the eyes of the players. There is also the traditional create-a-player mode.
One of the features in the game is a celebrity game involving Jamie Kennedy, Steve-O, David Arquette, Funkmaster Flex, or Carmen Electra which is initiated by a phone call from one of the aforementioned "celebrities" in the player's custom crib. The player plays against a celebrity with their own custom team of Pro Bowl players. The teams the celebrities use are The Buartville Funkmasters, Cincinnati Electra Shock, LA Dreamteam, Los Angeles Locos, and the Upper Darby Cheesesteaks. During the game, the celebrities appear in a small box and use trash-talk. If the player wins the game, they receive the team's stadium as a playable venue.
ESPN NFL 2K5 features the voices of Terry McGovern as play-by-play announcer Dan Stevens, Jay Styne as color commentator Peter O'Keefe, sideline reporter Suzy Kolber, studio host Chris Berman, Trey Wingo, and Mel Kiper Jr., with Berman appearing at the start of a player's own SportsCenter broadcast and during the loading screen for the player's own ESPN NFL Countdown pregame show, and Kolber appearing in the Player of the Game segment of the postgame show.