| Oct 3, 1980 | 1Alabama 45, Kentucky 0 | Box score |
| Oct 4, 1980 | App State 23, Marshall 6 | Box score |
| Oct 4, 1980 | Arizona 5, Iowa 3 | Box score |
| Oct 4, 1980 | 14Arkansas 44, TCU 7 | Box score |
| Oct 4, 1980 | Auburn 55, Richmond 16 | Box score |
| Oct 4, 1980 | 20Baylor 24, Houston 12 | Box score |
| Oct 4, 1980 | Bowling Green 17, Western Michigan 14upset | Box score |
| Oct 4, 1980 | Brown 28, Princeton 11 | Box score |
| Oct 4, 1980 | Central Michigan 14, Toledo 10 | Box score |
| Oct 4, 1980 | The Citadel 28, VMI 0 | Box score |
| Oct 4, 1980 | Clemson 13, Virginia Tech 10 | Box score |
| Oct 4, 1980 | Drake 30, Texas–Arlington 20upset | Box score |
| Oct 4, 1980 | 16Florida State 18, 3Nebraska 14upset | Box score |
| Oct 4, 1980 | Furman 42, Chattanooga 28 | Box score |
| Oct 4, 1980 | Harvard 15, Army 10 | Box score |
| Oct 4, 1980 | Holy Cross 17, Dartmouth 6 | Box score |
| Oct 4, 1980 | Indiana 31, Duke 21 | Box score |
| Oct 4, 1980 | Iowa State 69, Colorado State 0 | Box score |
| Oct 4, 1980 | Kansas 23, Syracuse 8upset | Box score |
| Oct 4, 1980 | Kent State 15, Ohio 14 | Box score |
| Oct 4, 1980 | LSU 24, 19Florida 7upset | Box score |
| Oct 4, 1980 | McNeese 24, Ball State 7 | Box score |
| Oct 4, 1980 | Memphis 24, Arkansas State 3 | Box score |
| Oct 4, 1980 | Michigan 38, California 13 | Box score |
| Oct 4, 1980 | Minnesota 49, Northwestern 21 | Box score |
| Oct 4, 1980 | Mississippi State 28, Illinois 21 | Box score |
| Oct 4, 1980 | Navy 21, Boston College 0 | Box score |
| Oct 4, 1980 | UNLV 36, Cal State Fullerton 17 | Box score |
| Oct 4, 1980 | New Mexico 24, Wyoming 21 | Box score |
| Oct 4, 1980 | 10North Carolina 33, Georgia Tech 0 | Box score |
| Oct 4, 1980 | North Texas 22, Louisiana 20 | Box score |
| Oct 4, 1980 | Northern Illinois 20, Southern Illinois 17 | Box score |
| Oct 4, 1980 | 7Notre Dame 26, Michigan State 21 | Box score |
| Oct 4, 1980 | 12Oklahoma 82, Colorado 42 | Box score |
| Oct 4, 1980 | Pacific 24, Washington State 22 | Box score |
| Oct 4, 1980 | 17Penn State 29, 9Missouri 21upset | Box score |
| Oct 4, 1980 | Pennsylvania 24, Columbia 13 | Box score |
| Oct 4, 1980 | 6Pittsburgh 38, Maryland 9 | Box score |
| Oct 4, 1980 | Purdue 28, Miami (OH) 3 | Box score |
| Oct 4, 1980 | Rutgers 44, Cornell 3 | Box score |
| Oct 4, 1980 | 18South Carolina 30, NC State 10 | Box score |
| Oct 4, 1980 | 4USC 23, Arizona State 21 | Box score |
| Oct 4, 1980 | SMU 31, Tulane 21 | Box score |
| Oct 4, 1980 | Southern Miss 28, Ole Miss 22 | Box score |
| Oct 4, 1980 | 15Stanford 35, San José State 21 | Box score |
| Oct 4, 1980 | Tennessee State 35, Long Beach State 18 | Box score |
| Oct 4, 1980 | 5Texas 41, Rice 28 | Box score |
| Oct 4, 1980 | Texas A&M 41, Texas Tech 21 | Box score |
| Oct 4, 1980 | UTEP 34, Hawai’i 14upset | Box score |
| Oct 4, 1980 | Tulsa 3, Kansas State 0 | Box score |
| Oct 4, 1980 | 11UCLA 17, 2Ohio State 0upset | Box score |
| Oct 4, 1980 | Utah 23, Utah State 19 | Box score |
| Oct 4, 1980 | Villanova 23, Cincinnati 6 | Box score |
| Oct 4, 1980 | Wake Forest 27, William & Mary 7 | Box score |
| Oct 4, 1980 | Washington 24, Oklahoma State 18 | Box score |
| Oct 4, 1980 | West Texas 17, New Mexico State 15 | Box score |
| Oct 4, 1980 | West Virginia 45, Virginia 21 | Box score |
| Oct 4, 1980 | Wichita State 46, Indiana State 20 | Box score |
| Oct 4, 1980 | Wisconsin 35, San Diego State 12 | Box score |
| Oct 4, 1980 | Yale 17, Air Force 16 | Box score |