| Sep 12, 1981 | 20Arizona State 52, Utah 10 | Box score |
| Sep 12, 1981 | Arkansas 14, Tulsa 10 | Box score |
| Sep 12, 1981 | Arkansas State 35, UL Monroe 13upset | Box score |
| Sep 12, 1981 | Ball State 24, McNeese 21 | Box score |
| Sep 12, 1981 | Baylor 38, Bowling Green 0 | Box score |
| Sep 12, 1981 | 15BYU 45, Air Force 21 | Box score |
| Sep 12, 1981 | Clemson 13, Tulane 5 | Box score |
| Sep 12, 1981 | Colorado 45, Texas Tech 27 | Box score |
| Sep 12, 1981 | Drake 17, Indiana State 14 | Box score |
| Sep 12, 1981 | Florida 35, Furman 7 | Box score |
| Sep 12, 1981 | 18Florida State 10, Memphis 5 | Box score |
| Sep 12, 1981 | 6Georgia 27, California 13 | Box score |
| Sep 12, 1981 | Georgia Tech 24, 2Alabama 21upset | Box score |
| Sep 12, 1981 | Illinois 27, Michigan State 17 | Box score |
| Sep 12, 1981 | Indiana 21, Northwestern 20 | Box score |
| Sep 12, 1981 | Iowa 10, 7Nebraska 7upset | Box score |
| Sep 12, 1981 | Iowa State 17, West Texas 13 | Box score |
| Sep 12, 1981 | Kansas 19, Oregon 10 | Box score |
| Sep 12, 1981 | Long Beach State 17, Northern Illinois 7 | Box score |
| Sep 12, 1981 | Louisville 31, Toledo 6 | Box score |
| Sep 12, 1981 | Miami (OH) 33, William & Mary 14 | Box score |
| Sep 12, 1981 | Minnesota 19, Ohio 17 | Box score |
| Sep 12, 1981 | Ole Miss 20, South Carolina 13upset | Box score |
| Sep 12, 1981 | Missouri 24, Army 10 | Box score |
| Sep 12, 1981 | Navy 17, The Citadel 7 | Box score |
| Sep 12, 1981 | UNLV 49, New Mexico 42 | Box score |
| Sep 12, 1981 | 13North Carolina 56, East Carolina 0 | Box score |
| Sep 12, 1981 | NC State 28, Wake Forest 23 | Box score |
| Sep 12, 1981 | 4Notre Dame 27, LSU 9 | Box score |
| Sep 12, 1981 | 11Ohio State 34, Duke 13 | Box score |
| Sep 12, 1981 | 3Oklahoma 37, Wyoming 20 | Box score |
| Sep 12, 1981 | Oregon State 31, Fresno State 28 | Box score |
| Sep 12, 1981 | 9Penn State 52, Cincinnati 0 | Box score |
| Sep 12, 1981 | Purdue 27, 19Stanford 19upset | Box score |
| Sep 12, 1981 | Rutgers 13, Colgate 5 | Box score |
| Sep 12, 1981 | San Diego State 30, Colorado State 14 | Box score |
| Sep 12, 1981 | 5USC 43, Tennessee 7 | Box score |
| Sep 12, 1981 | SMU 34, North Texas 7 | Box score |
| Sep 12, 1981 | Temple 31, Syracuse 19 | Box score |
| Sep 12, 1981 | 8Texas 31, Rice 3 | Box score |
| Sep 12, 1981 | Texas–Arlington 26, New Mexico State 13 | Box score |
| Sep 12, 1981 | 12UCLA 35, Arizona 18 | Box score |
| Sep 12, 1981 | Utah State 14, Cal State Fullerton 9 | Box score |
| Sep 12, 1981 | Vanderbilt 23, Maryland 17upset | Box score |
| Sep 12, 1981 | VMI 21, Western Carolina 14 | Box score |
| Sep 12, 1981 | Virginia Tech 28, Richmond 12 | Box score |
| Sep 12, 1981 | 17Washington 34, Pacific 14 | Box score |
| Sep 12, 1981 | West Virginia 32, Virginia 18 | Box score |
| Sep 12, 1981 | Western Michigan 20, Kent State 17 | Box score |
| Sep 12, 1981 | Wichita State 13, Southern Illinois 7 | Box score |
| Sep 12, 1981 | Wisconsin 21, 1Michigan 14upset | Box score |