- Release date: August 10, 2010 (Based on the 2010 NFL season.)
- Cover athlete: Drew Brees QB New Orleans Saints (PS2, PS3, PSP, Wii, Xbox 360, iOS, Android)
- 99 Overall Club: QB Peyton Manning (Colts), QB Drew Brees (Saints), RB Chris Johnson (Titans), RE Jared Allen (Vikings), MLB Patrick Willis (49ers), CB Darrelle Revis (Jets)
- Arizona Cardinals QB Matt Leinart signed with the Houston Texans in Roster Update #3.
- Miami Dolphins QB Pat White was released in Roster Update #3.
- Buffalo Bills QB Trent Edwards signed with the Jacksonville Jaguars in Roster Update #6.