- Release date: August 31, 1999 (Based on on the 1999 NFL season.)
- Cover athlete: John Madden (Game Boy Color, Nintendo 64, PlayStation, Windows PC)
- The Cleveland Browns are now back in the game after not having a team for the past 3 NFL seasons.
- 100 Overall Club: FB Mike Alstott (Buccaneers), CB Deion Sanders (Cowboys)
- 99 Overall Club: RB Barry Sanders (Lions), C Dermontti Dawson (Steelers), P Matt Turk (Redskins)
- A limited number of players or their names can now be either created or edited as modified roster.