| 8/28/2021 | Nebraska | 22 | at | Illinois | 30 | |||
| 9/2/2021 | Ohio State | 45 | at | Minnesota | 31 | |||
| 9/3/2021 | Michigan State | 38 | at | Northwestern | 21 | |||
| 9/4/2021 | Texas-San Antonio | 37 | at | Illinois | 30 | CUSA | ||
| Indiana | 6 | at | Iowa | 34 | ||||
| West Virginia | 24 | at | Maryland | 30 | B12 | |||
| Western Michigan | 14 | at | Michigan | 47 | MAC | |||
| Fordham | 7 | at | Nebraska | 52 | Pat (1AA) | |||
| Oregon State | 21 | at | Purdue | 30 | P12 | |||
| Temple | 14 | at | Rutgers | 61 | AAC | |||
| Penn State | 16 | at | Wisconsin | 10 | ||||
| 9/11/2021 | Purdue | 49 | at | Connecticut | 0 | @ Ind | ||
| Idaho | 14 | at | Indiana | 56 | BSky (1AA) | |||
| Iowa | 27 | at | Iowa State | 17 | @ B12 | |||
| Howard | 0 | at | Maryland | 62 | MEAC (1AA) | |||
| Washington | 10 | at | Michigan | 31 | P12 | |||
| Youngstown State | 14 | at | Michigan State | 42 | MVC (1AA) | |||
| Miami-Ohio | 26 | at | Minnesota | 31 | MAC | |||
| Buffalo | 3 | at | Nebraska | 28 | MAC | |||
| Indiana State | 6 | at | Northwestern | 24 | MVC (1AA) | |||
| Oregon | 35 | at | Ohio State | 28 | P12 | |||
| Ball State | 13 | at | Penn State | 44 | MAC | |||
| Rutgers | 17 | at | Syracuse | 7 | @ ACC | |||
| Illinois | 14 | at | Virginia | 42 | @ ACC | |||
| Eastern Michigan | 7 | at | Wisconsin | 34 | MAC | |||
| 9/17/2021 | Maryland | 20 | at | Illinois | 17 | |||
| 9/18/2021 | Minnesota | 30 | at | Colorado | 0 | @ P12 | ||
| Northwestern | 23 | at | Duke | 30 | @ ACC | |||
| Cincinnati | 38 | at | Indiana | 24 | AAC | |||
| Kent State | 7 | at | Iowa | 30 | MAC | |||
| Michigan State | 38 | at | Miami-Florida | 17 | @ ACC | |||
| Northern Illinois | 10 | at | Michigan | 63 | MAC | |||
| Purdue | 13 | at | Notre Dame | 27 | @ ND | |||
| Tulsa | 20 | at | Ohio State | 41 | AAC | |||
| Nebraska | 16 | at | Oklahoma | 23 | @ B12 | |||
| Auburn | 20 | at | Penn State | 28 | SEC | |||
| Delaware | 13 | at | Rutgers | 45 | CAAF (1AA) | |||
| 9/25/2021 | Colorado State | 14 | at | Iowa | 24 | MW | ||
| Kent State | 16 | at | Maryland | 37 | MAC | |||
| Rutgers | 13 | at | Michigan | 20 | ||||
| Nebraska | 20 | at | Michigan State | 23 | OT | |||
| Bowling Green | 14 | at | Minnesota | 10 | MAC | |||
| Ohio | 6 | at | Northwestern | 35 | MAC | |||
| Akron | 7 | at | Ohio State | 59 | MAC | |||
| Villanova | 17 | at | Penn State | 38 | CAAF (1AA) | |||
| Illinois | 9 | at | Purdue | 13 | ||||
| Indiana | 33 | at | Western Kentucky | 31 | @ CUSA | |||
| Notre Dame | 41 | vs | Wisconsin | 13 | Chicago IL | vs ND | ||
| 10/1/2021 | Iowa | 51 | at | Maryland | 14 | |||
| 10/2/2021 | UNC-Charlotte | 14 | at | Illinois | 24 | CUSA | ||
| Western Kentucky | 31 | at | Michigan State | 48 | CUSA | |||
| Northwestern | 7 | at | Nebraska | 56 | ||||
| Indiana | 0 | at | Penn State | 24 | ||||
| Minnesota | 20 | at | Purdue | 13 | ||||
| Ohio State | 52 | at | Rutgers | 13 | ||||
| Michigan | 38 | at | Wisconsin | 17 | ||||
| 10/9/2021 | Wisconsin | 24 | at | Illinois | 0 | |||
| Penn State | 20 | at | Iowa | 23 | ||||
| Michigan | 32 | at | Nebraska | 29 | ||||
| Maryland | 17 | at | Ohio State | 66 | ||||
| Michigan State | 31 | at | Rutgers | 13 | ||||
| 10/16/2021 | Michigan State | 20 | at | Indiana | 15 | |||
| Purdue | 24 | at | Iowa | 7 | ||||
| Nebraska | 23 | at | Minnesota | 30 | ||||
| Rutgers | 7 | at | Northwestern | 21 | ||||
| Army | 14 | at | Wisconsin | 20 | Ind | |||
| 10/23/2021 | Ohio State | 54 | at | Indiana | 7 | |||
| Northwestern | 7 | at | Michigan | 33 | ||||
| Maryland | 16 | at | Minnesota | 34 | ||||
| Illinois | 20 | at | Penn State | 18 | 9OT | |||
| Wisconsin | 30 | at | Purdue | 13 | ||||
| 10/30/2021 | Rutgers | 20 | at | Illinois | 14 | |||
| Indiana | 35 | at | Maryland | 38 | ||||
| Michigan | 33 | at | Michigan State | 37 | ||||
| Purdue | 28 | at | Nebraska | 23 | ||||
| Minnesota | 41 | at | Northwestern | 14 | ||||
| Penn State | 24 | at | Ohio State | 33 | ||||
| Iowa | 7 | at | Wisconsin | 27 | ||||
| 11/6/2021 | Penn State | 31 | at | Maryland | 14 | |||
| Indiana | 7 | at | Michigan | 29 | ||||
| Illinois | 14 | at | Minnesota | 6 | ||||
| Ohio State | 26 | at | Nebraska | 17 | ||||
| Iowa | 17 | at | Northwestern | 12 | ||||
| Michigan State | 29 | at | Purdue | 40 | ||||
| Wisconsin | 52 | at | Rutgers | 3 | ||||
| 11/13/2021 | Rutgers | 38 | at | Indiana | 3 | |||
| Minnesota | 22 | at | Iowa | 27 | ||||
| Maryland | 21 | at | Michigan State | 40 | ||||
| Purdue | 31 | at | Ohio State | 59 | ||||
| Michigan | 21 | at | Penn State | 17 | ||||
| Northwestern | 7 | at | Wisconsin | 35 | ||||
| 11/20/2021 | Minnesota | 35 | at | Indiana | 14 | |||
| Illinois | 23 | at | Iowa | 33 | ||||
| Michigan | 59 | at | Maryland | 18 | ||||
| Purdue | 32 | at | Northwestern | 14 | ||||
| Michigan State | 7 | at | Ohio State | 56 | ||||
| Rutgers | 0 | at | Penn State | 28 | ||||
| Nebraska | 28 | at | Wisconsin | 35 | ||||
| 11/26/2021 | Iowa | 28 | at | Nebraska | 21 | |||
| 11/27/2021 | Northwestern | 14 | at | Illinois | 47 | |||
| Ohio State | 27 | at | Michigan | 42 | ||||
| Penn State | 27 | at | Michigan State | 30 | ||||
| Wisconsin | 13 | at | Minnesota | 23 | ||||
| Indiana | 7 | at | Purdue | 44 | ||||
| Maryland | 40 | at | Rutgers | 16 | ||||
| 12/4/2021 | Michigan | 42 | vs | Iowa | 3 | Big 10 Championship - Indianapolis IN | ||
| 12/28/2021 | West Virginia | 6 | vs | Minnesota | 18 | Guaranteed Rate Bowl - Phoenix AZ | vs B12 | |
| 12/29/2021 | Maryland | 54 | vs | Virginia Tech | 10 | Pinstribe Bowl - Bronx NY | vs ACC | |
| 12/30/2021 | Wisconsin | 20 | vs | Arizona State | 13 | Las Vegas Bowl - Las Vegas NV | vs P12 | |
| Pittsburgh | 21 | vs | Michigan State | 31 | Peach Bowl - Atlanta GA | vs ACC | ||
| Tennessee | 45 | vs | Purdue | 48 | OT | Music City Bowl - Nashville TN | vs SEC | |
| 12/31/2021 | Georgia | 34 | vs | Michigan | 11 | FBS Semifinal - Miami Gardens FL | vs SEC | |
| Wake Forest | 38 | vs | Rutgers | 10 | Gator Bowl - Jacksonville FL | vs ACC | ||
| 1/1/2022 | Penn State | 10 | vs | Arkansas | 24 | Outback Bowl - Tampa FL | vs SEC | |
| Iowa | 17 | vs | Kentucky | 20 | Citrus Bowl - Orlando FL | vs SEC | ||
| Utah | 45 | vs | Ohio State | 48 | Rose Bowl - Pasadena CA | vs P12 |