| Sep 26, 1981 | 10Alabama 28, Vanderbilt 7 | Box score |
| Sep 26, 1981 | Arizona 37, Cal State Fullerton 16 | Box score |
| Sep 26, 1981 | Arkansas 27, Ole Miss 13 | Box score |
| Sep 26, 1981 | Arkansas State 26, Central Michigan 23upset | Box score |
| Sep 26, 1981 | Army 23, Brown 17 | Box score |
| Sep 26, 1981 | Baylor 28, Texas Tech 15 | Box score |
| Sep 26, 1981 | 11BYU 41, Colorado 20 | Box score |
| Sep 26, 1981 | Cincinnati 10, Rutgers 0upset | Box score |
| Sep 26, 1981 | The Citadel 34, App State 20 | Box score |
| Sep 26, 1981 | Colgate 34, Cornell 10 | Box score |
| Sep 26, 1981 | Drake 18, Kansas State 17 | Box score |
| Sep 26, 1981 | Duke 29, Virginia 24 | Box score |
| Sep 26, 1981 | East Carolina 28, Toledo 24 | Box score |
| Sep 26, 1981 | Furman 31, Western Carolina 27 | Box score |
| Sep 26, 1981 | 17Georgia 24, South Carolina 0 | Box score |
| Sep 26, 1981 | Holy Cross 33, Harvard 19upset | Box score |
| Sep 26, 1981 | Houston 35, Utah State 7 | Box score |
| Sep 26, 1981 | Iowa 20, 6UCLA 7upset | Box score |
| Sep 26, 1981 | Iowa State 28, Kent State 19 | Box score |
| Sep 26, 1981 | Kansas 21, Kentucky 16 | Box score |
| Sep 26, 1981 | Louisiana 34, North Texas 11 | Box score |
| Sep 26, 1981 | LSU 28, Rice 14 | Box score |
| Sep 26, 1981 | Maryland 34, NC State 9upset | Box score |
| Sep 26, 1981 | Memphis 28, Georgia Tech 15upset | Box score |
| Sep 26, 1981 | Miami (OH) 18, Eastern Michigan 12 | Box score |
| Sep 26, 1981 | 7Michigan 21, Navy 16 | Box score |
| Sep 26, 1981 | Michigan State 10, Bowling Green 7 | Box score |
| Sep 26, 1981 | Minnesota 42, Oregon State 12 | Box score |
| Sep 26, 1981 | 12Mississippi State 28, Florida 7 | Box score |
| Sep 26, 1981 | Missouri 34, Louisville 3 | Box score |
| Sep 26, 1981 | UNLV 32, Long Beach State 31 | Box score |
| Sep 26, 1981 | New Mexico 27, Air Force 10 | Box score |
| Sep 26, 1981 | 9North Carolina 56, Boston College 14 | Box score |
| Sep 26, 1981 | Northern Illinois 40, Illinois State 7 | Box score |
| Sep 26, 1981 | Ohio 30, Ball State 27 | Box score |
| Sep 26, 1981 | 8Ohio State 24, Stanford 19 | Box score |
| Sep 26, 1981 | 3Penn State 30, 15Nebraska 24 | Box score |
| Sep 26, 1981 | Purdue 15, 13Notre Dame 14upset | Box score |
| Sep 26, 1981 | San Diego State 23, Oklahoma State 16 | Box score |
| Sep 26, 1981 | San José State 27, California 24 | Box score |
| Sep 26, 1981 | 1USC 28, 2Oklahoma 24 | Box score |
| Sep 26, 1981 | Southern Illinois 36, Tulsa 34upset | Box score |
| Sep 26, 1981 | 20SMU 20, TCU 9 | Box score |
| Sep 26, 1981 | Southern Miss 17, Richmond 10 | Box score |
| Sep 26, 1981 | Syracuse 21, Indiana 7 | Box score |
| Sep 26, 1981 | Tennessee 10, Auburn 7 | Box score |
| Sep 26, 1981 | 4Texas 14, 14Miami 7 | Box score |
| Sep 26, 1981 | Texas A&M 43, Louisiana Tech 7 | Box score |
| Sep 26, 1981 | Utah 42, Northwestern 0 | Box score |
| Sep 26, 1981 | Virginia Tech 30, Wake Forest 14 | Box score |
| Sep 26, 1981 | 16Washington 17, Oregon 3 | Box score |
| Sep 26, 1981 | Washington State 24, 18Arizona State 21upset | Box score |
| Sep 26, 1981 | West Texas 35, Texas–Arlington 31 | Box score |
| Sep 26, 1981 | West Virginia 49, Colorado State 3 | Box score |
| Sep 26, 1981 | Indiana State 14, Wichita State 14 | Box score |
| Sep 26, 1981 | Wisconsin 21, Western Michigan 10 | Box score |