| Oct 25, 1980 | 1Alabama 42, 20Southern Miss 7 | Box score |
| Oct 25, 1980 | Arizona State 37, Pacific 9 | Box score |
| Oct 25, 1980 | 11Baylor 21, TCU 6 | Box score |
| Oct 25, 1980 | Boston College 30, Army 14 | Box score |
| Oct 25, 1980 | 19BYU 34, Hawai’i 7 | Box score |
| Oct 25, 1980 | Brown 21, Holy Cross 3 | Box score |
| Oct 25, 1980 | Colgate 35, Columbia 22 | Box score |
| Oct 25, 1980 | Utah 21, Colorado State 21 | Box score |
| Oct 25, 1980 | Cornell 7, Dartmouth 3 | Box score |
| Oct 25, 1980 | Drake 28, New Mexico State 22 | Box score |
| Oct 25, 1980 | Florida 13, Louisville 0 | Box score |
| Oct 25, 1980 | 6Florida State 24, Memphis 3 | Box score |
| Oct 25, 1980 | Furman 21, App State 20 | Box score |
| Oct 25, 1980 | 5Georgia 27, Kentucky 0 | Box score |
| Oct 25, 1980 | Houston 24, 15Arkansas 17upset | Box score |
| Oct 25, 1980 | Illinois State 9, Indiana State 0upset | Box score |
| Oct 25, 1980 | Indiana 35, Northwestern 20 | Box score |
| Oct 25, 1980 | Oklahoma State 14, Kansas 14 | Box score |
| Oct 25, 1980 | Kent State 35, Eastern Michigan 12 | Box score |
| Oct 25, 1980 | Long Beach State 31, Oregon State 21 | Box score |
| Oct 25, 1980 | Louisiana 38, Lamar 10 | Box score |
| Oct 25, 1980 | Western Carolina 13, Marshall 13 | Box score |
| Oct 25, 1980 | Maryland 17, Duke 14 | Box score |
| Oct 25, 1980 | McNeese 36, Arkansas State 28 | Box score |
| Oct 25, 1980 | Miami (OH) 7, Bowling Green 3 | Box score |
| Oct 25, 1980 | Michigan 45, Illinois 14 | Box score |
| Oct 25, 1980 | Minnesota 24, Iowa 6 | Box score |
| Oct 25, 1980 | Ole Miss 27, Vanderbilt 14 | Box score |
| Oct 25, 1980 | Mississippi State 24, Auburn 21 | Box score |
| Oct 25, 1980 | 16Missouri 13, Kansas State 3 | Box score |
| Oct 25, 1980 | Navy 24, 18Washington 10upset | Box score |
| Oct 25, 1980 | 9Nebraska 45, Colorado 7 | Box score |
| Oct 25, 1980 | New Mexico 22, UTEP 21 | Box score |
| Oct 25, 1980 | 7North Carolina 31, East Carolina 3 | Box score |
| Oct 25, 1980 | NC State 24, Clemson 20 | Box score |
| Oct 25, 1980 | Northern Illinois 17, Wichita State 14 | Box score |
| Oct 25, 1980 | 4Notre Dame 20, Arizona 3 | Box score |
| Oct 25, 1980 | Ohio 24, Toledo 9 | Box score |
| Oct 25, 1980 | 10Ohio State 21, Wisconsin 0 | Box score |
| Oct 25, 1980 | 17Oklahoma 42, Iowa State 7 | Box score |
| Oct 25, 1980 | Oregon 32, UNLV 9 | Box score |
| Oct 25, 1980 | 13Penn State 20, West Virginia 15 | Box score |
| Oct 25, 1980 | 12Pittsburgh 30, Tennessee 6 | Box score |
| Oct 25, 1980 | Princeton 7, Harvard 3 | Box score |
| Oct 25, 1980 | Purdue 36, Michigan State 25 | Box score |
| Oct 25, 1980 | Rice 10, Texas A&M 6upset | Box score |
| Oct 25, 1980 | Richmond 18, Virginia Tech 7upset | Box score |
| Oct 25, 1980 | SMU 20, 2Texas 6upset | Box score |
| Oct 25, 1980 | Stanford 48, Washington State 34 | Box score |
| Oct 25, 1980 | Syracuse 17, Rutgers 9 | Box score |
| Oct 25, 1980 | Temple 23, Cincinnati 7 | Box score |
| Oct 25, 1980 | Texas–Arlington 21, Louisiana Tech 20 | Box score |
| Oct 25, 1980 | Tulane 31, Georgia Tech 14 | Box score |
| Oct 25, 1980 | Tulsa 44, West Texas 24 | Box score |
| Oct 25, 1980 | 3UCLA 32, California 9 | Box score |
| Oct 25, 1980 | Utah State 14, Fresno State 0 | Box score |
| Oct 25, 1980 | Villanova 17, VMI 6 | Box score |
| Oct 25, 1980 | Virginia 24, Wake Forest 21upset | Box score |
| Oct 25, 1980 | Western Michigan 17, Ball State 15 | Box score |
| Oct 25, 1980 | Wyoming 34, San Diego State 9 | Box score |
| Oct 25, 1980 | Yale 8, Pennsylvania 0 | Box score |