| Oct 2, 1981 | 10BYU 32, Utah State 26 | Box score |
| Oct 2, 1981 | Utah 38, UTEP 10 | Box score |
| Oct 3, 1981 | Air Force 28, Colorado State 14 | Box score |
| Oct 3, 1981 | 11Alabama 38, Ole Miss 7 | Box score |
| Oct 3, 1981 | Arizona 17, Stanford 13 | Box score |
| Oct 3, 1981 | Arizona State 26, 12Washington 7upset | Box score |
| Oct 3, 1981 | Army 27, Harvard 13upset | Box score |
| Oct 3, 1981 | Ball State 23, Northern Illinois 0 | Box score |
| Oct 3, 1981 | Central Michigan 63, Eastern Michigan 14 | Box score |
| Oct 3, 1981 | Chattanooga 31, Furman 28 | Box score |
| Oct 3, 1981 | 14Clemson 21, Kentucky 3 | Box score |
| Oct 3, 1981 | Columbia 20, Pennsylvania 9 | Box score |
| Oct 3, 1981 | Drake 18, Long Beach State 7 | Box score |
| Oct 3, 1981 | Duke 24, East Carolina 14 | Box score |
| Oct 3, 1981 | Florida 24, LSU 10 | Box score |
| Oct 3, 1981 | Florida State 36, 7Ohio State 27upset | Box score |
| Oct 3, 1981 | Holy Cross 28, Dartmouth 0 | Box score |
| Oct 3, 1981 | Houston 24, Baylor 3 | Box score |
| Oct 3, 1981 | Illinois 38, Minnesota 29 | Box score |
| Oct 3, 1981 | 18Iowa 64, Northwestern 0 | Box score |
| Oct 3, 1981 | 5Oklahoma 7, 20Iowa State 7 | Box score |
| Oct 3, 1981 | Kansas 17, Arkansas State 16 | Box score |
| Oct 3, 1981 | UL Monroe 35, Louisiana Tech 0 | Box score |
| Oct 3, 1981 | Louisville 36, Marshall 0 | Box score |
| Oct 3, 1981 | 17Miami 48, Vanderbilt 16 | Box score |
| Oct 3, 1981 | Miami (OH) 20, Kent State 13 | Box score |
| Oct 3, 1981 | 8Michigan 38, Indiana 17 | Box score |
| Oct 3, 1981 | Missouri 14, 9Mississippi State 3upset | Box score |
| Oct 3, 1981 | Nebraska 17, Auburn 3 | Box score |
| Oct 3, 1981 | 6North Carolina 28, Georgia Tech 7 | Box score |
| Oct 3, 1981 | NC State 30, Virginia 24 | Box score |
| Oct 3, 1981 | Notre Dame 20, Michigan State 7 | Box score |
| Oct 3, 1981 | Oklahoma State 9, North Texas 0 | Box score |
| Oct 3, 1981 | 2Penn State 30, Temple 0 | Box score |
| Oct 3, 1981 | 4Pittsburgh 42, South Carolina 28 | Box score |
| Oct 3, 1981 | Princeton 20, Brown 17upset | Box score |
| Oct 3, 1981 | Rice 20, Tulane 16 | Box score |
| Oct 3, 1981 | Rutgers 31, Cornell 17 | Box score |
| Oct 3, 1981 | San Diego State 17, New Mexico 15 | Box score |
| Oct 3, 1981 | San José State 65, Fresno State 33 | Box score |
| Oct 3, 1981 | 1USC 56, Oregon State 22 | Box score |
| Oct 3, 1981 | Southern Illinois 14, Illinois State 3 | Box score |
| Oct 3, 1981 | Southern Miss 52, Texas–Arlington 9 | Box score |
| Oct 3, 1981 | Maryland 17, Syracuse 17 | Box score |
| Oct 3, 1981 | Texas A&M 24, Texas Tech 23 | Box score |
| Oct 3, 1981 | TCU 28, 19Arkansas 24upset | Box score |
| Oct 3, 1981 | Toledo 21, Ohio 14 | Box score |
| Oct 3, 1981 | Tulsa 35, Kansas State 21 | Box score |
| Oct 3, 1981 | 16UCLA 27, Colorado 7 | Box score |
| Oct 3, 1981 | VMI 31, William & Mary 14 | Box score |
| Oct 3, 1981 | Virginia Tech 17, Memphis 13 | Box score |
| Oct 3, 1981 | Wake Forest 15, App State 14 | Box score |
| Oct 3, 1981 | Washington State 31, Pacific 0 | Box score |
| Oct 3, 1981 | West Texas 31, McNeese 24upset | Box score |
| Oct 3, 1981 | West Virginia 38, Boston College 10 | Box score |
| Oct 3, 1981 | Western Michigan 21, Bowling Green 7 | Box score |
| Oct 3, 1981 | Wichita State 24, New Mexico State 20 | Box score |
| Oct 3, 1981 | Wisconsin 20, Purdue 14 | Box score |
| Oct 3, 1981 | Wyoming 45, UNLV 21 | Box score |
| Oct 3, 1981 | Yale 23, Navy 19 | Box score |