| Date | Opponent | Time | TV | Result | Record | |
|---|---|---|---|---|---|---|
 | 09/04/10 | vs. Eastern Illinois | 11:00 AM | BTN | W 37-7 | 1-0 |
 | 09/11/10 | vs. Iowa State | 2:30 PM | ABC&ESPN2 | W 35-7 | 2-0 |
 | 09/18/10 | at Arizona | 9:30 PM | ESPN | L 27-34 | 2-1 |
 | 09/25/10 | vs. Ball State | 11:00 AM | BTN | W 45-0 | 3-1 |
 | 10/02/10 | vs. Penn State | 7:05 PM | ESPN | W 24-3 | 4-1 (1-0) |
 | 10/16/10 | at Michigan | 2:30 PM | ABC | W 38-28 | 5-1 (2-0) |
 | 10/23/10 | vs. Wisconsin | 2:30 PM | ABC | L 30-31 | 5-2 (2-1) |
 | 10/30/10 | vs. Michigan State | 2:30 PM | ABC | W 37-6 | 6-2 (3-1) |
 | 11/06/10 | at Indiana | 11:00 AM | BTN | W 18-13 | 7-2 (4-1) |
 | 11/13/10 | at Northwestern | 11:00 AM | ESPN/ESPN2 | L 17-21 | 7-3 (4-2) |
 | 11/20/10 | vs. Ohio State | 2:30 PM | ABC | L 17-20 | 7-4 (4-3) |
 | 11/27/10 | at Minnesota | 2:30 PM | BTN | L 24-27 | 7-5 (4-4) |
 | 12/28/10 | vs. Missouri | 9:00 PM | ESPN | W 27-24 | 8-5 (4-4) |