| Sep 25, 1959 | George Washington 18, Boston University 14upset | Box score |
| Sep 25, 1959 | Iowa State 28, Denver 12 | Box score |
| Sep 25, 1959 | Miami 26, Tulane 7 | Box score |
| Sep 25, 1959 | 11USC 23, Pittsburgh 0 | Box score |
| Sep 26, 1959 | Air Force 20, Wyoming 7 | Box score |
| Sep 26, 1959 | Alabama 3, Houston 0 | Box score |
| Sep 26, 1959 | Arizona 7, West Texas 6 | Box score |
| Sep 26, 1959 | Arizona State 34, Utah State 12 | Box score |
| Sep 26, 1959 | Arkansas 13, Oklahoma State 7 | Box score |
| Sep 26, 1959 | 7Army 44, Boston College 8 | Box score |
| Sep 26, 1959 | Baylor 15, Colorado 7 | Box score |
| Sep 26, 1959 | Cincinnati 21, Dayton 7 | Box score |
| Sep 26, 1959 | 5Clemson 47, Virginia 0 | Box score |
| Sep 26, 1959 | Colorado State 14, New Mexico 9 | Box score |
| Sep 26, 1959 | Columbia 21, Brown 6upset | Box score |
| Sep 26, 1959 | Cornell 20, Colgate 15 | Box score |
| Sep 26, 1959 | Detroit Mercy 14, Marquette 0 | Box score |
| Sep 26, 1959 | 19Florida 14, Mississippi State 13 | Box score |
| Sep 26, 1959 | Florida State 47, The Citadel 6 | Box score |
| Sep 26, 1959 | 17Georgia 21, Vanderbilt 6 | Box score |
| Sep 26, 1959 | 16Georgia Tech 16, 6SMU 12upset | Box score |
| Sep 26, 1959 | Holy Cross 31, Dartmouth 8upset | Box score |
| Sep 26, 1959 | Indiana 20, Illinois 0 | Box score |
| Sep 26, 1959 | 13Iowa 42, California 12 | Box score |
| Sep 26, 1959 | 1LSU 10, 9TCU 0 | Box score |
| Sep 26, 1959 | 4Ole Miss 16, Kentucky 0 | Box score |
| Sep 26, 1959 | Missouri 20, Michigan 15 | Box score |
| Sep 26, 1959 | 13Navy 29, William & Mary 2 | Box score |
| Sep 26, 1959 | Nebraska 32, Minnesota 12upset | Box score |
| Sep 26, 1959 | North Texas 31, UTEP 7 | Box score |
| Sep 26, 1959 | 10Northwestern 45, 2Oklahoma 13upset | Box score |
| Sep 26, 1959 | Notre Dame 28, North Carolina 8 | Box score |
| Sep 26, 1959 | 12Ohio State 14, Duke 13 | Box score |
| Sep 26, 1959 | Oregon 21, Utah 6 | Box score |
| Sep 26, 1959 | 18Penn State 21, VMI 0 | Box score |
| Sep 26, 1959 | Rutgers 8, Princeton 6 | Box score |
| Sep 26, 1959 | Syracuse 35, Kansas 21 | Box score |
| Sep 26, 1959 | Tennessee 3, 3Auburn 0upset | Box score |
| Sep 26, 1959 | 15Texas 26, Maryland 0 | Box score |
| Sep 26, 1959 | Texas A&M 9, Michigan State 7 | Box score |
| Sep 26, 1959 | Texas Tech 15, Oregon State 14 | Box score |
| Sep 26, 1959 | Tulsa 28, New Mexico State 27 | Box score |
| Sep 26, 1959 | Wake Forest 27, Virginia Tech 18 | Box score |
| Sep 26, 1959 | Washington 23, Idaho 0 | Box score |
| Sep 26, 1959 | Washington State 30, San José State 6 | Box score |
| Sep 26, 1959 | West Virginia 10, Richmond 7 | Box score |
| Sep 26, 1959 | Wichita State 27, Hardin Simmons 13 | Box score |
| Sep 26, 1959 | 8Wisconsin 16, Stanford 14 | Box score |
| Sep 27, 1959 | Xavier 48, Villanova 20 | Box score |