| Sep 30, 1921 | Chattanooga 53, Bryson 0 | Box score |
| Oct 1, 1921 | Amherst 9, Columbia 7upset | Box score |
| Oct 1, 1921 | Arkansas 28, Hendrix 0 | Box score |
| Oct 1, 1921 | Auburn 35, Samford 3 | Box score |
| Oct 1, 1921 | Baylor 17, Austin 13 | Box score |
| Oct 1, 1921 | Brown 12, Colby 7 | Box score |
| Oct 1, 1921 | California 14, Olympic Club 0 | Box score |
| Oct 1, 1921 | The Citadel 37, Parris Island Marines 0 | Box score |
| Oct 1, 1921 | Colgate 14, Allegheny 0 | Box score |
| Oct 1, 1921 | Cornell 41, St. Bonaventure 0 | Box score |
| Oct 1, 1921 | Dartmouth 28, Middlebury 3 | Box score |
| Oct 1, 1921 | Davidson 7, Presbyterian 0 | Box score |
| Oct 1, 1921 | Denver 41, Fort Hays 7 | Box score |
| Oct 1, 1921 | Florida 6, Fort Benning 0 | Box score |
| Oct 1, 1921 | Grinnell 35, Simpson (IA) 0 | Box score |
| Oct 1, 1921 | Hardin Simmons 10, TCU 7upset | Box score |
| Oct 1, 1921 | Indiana 29, Kalamazoo 0 | Box score |
| Oct 1, 1921 | Iowa 52, Knox 14 | Box score |
| Oct 1, 1921 | Iowa State 28, Coe 3 | Box score |
| Oct 1, 1921 | Kansas 28, Washburn 7 | Box score |
| Oct 1, 1921 | Kansas State 7, Emporia College 3 | Box score |
| Oct 1, 1921 | Kentucky 68, Kentucky Wesleyan 0 | Box score |
| Oct 1, 1921 | Lehigh 22, Susquehanna 0 | Box score |
| Oct 1, 1921 | Michigan 44, Mount Union 0 | Box score |
| Oct 1, 1921 | Minnesota 19, North Dakota 0 | Box score |
| Oct 1, 1921 | Ole Miss 82, Memphis 0 | Box score |
| Oct 1, 1921 | Nebraska 55, Nebraska Wesleyan 0 | Box score |
| Oct 1, 1921 | Notre Dame 57, DePauw 10 | Box score |
| Oct 1, 1921 | Ohio State 28, Ohio Wesleyan 0 | Box score |
| Oct 1, 1921 | Oregon 7, Willamette 3 | Box score |
| Oct 1, 1921 | Oregon State 68, Chemawa 0 | Box score |
| Oct 1, 1921 | Penn State 24, Gettysburg 0 | Box score |
| Oct 1, 1921 | Pennsylvania 20, Franklin & Marshall 0 | Box score |
| Oct 1, 1921 | Phillips 42, Kingfisher 7 | Box score |
| Oct 1, 1921 | Princeton 21, Swarthmore 7 | Box score |
| Oct 1, 1921 | Rice 54, Louisiana 0 | Box score |
| Oct 1, 1921 | Richmond 14, Catholic 0 | Box score |
| Oct 1, 1921 | Sewanee 26, Cumberland (TN) 0 | Box score |
| Oct 1, 1921 | SMU 3, Howard Payne 0 | Box score |
| Oct 1, 1921 | Stanford 41, U.S. Marines 0 | Box score |
| Oct 1, 1921 | Syracuse 38, Ohio 0 | Box score |
| Oct 1, 1921 | Tennessee 7, Maryville (TN) 0 | Box score |
| Oct 1, 1921 | Texas 33, St. Edward’s 0 | Box score |
| Oct 1, 1921 | Texas State 10, Southwestern U 0upset | Box score |
| Oct 1, 1921 | Vanderbilt 34, Middle Tennessee 0 | Box score |
| Oct 1, 1921 | Virginia 28, George Washington 0 | Box score |
| Oct 1, 1921 | VMI 32, Hampden Sydney 0 | Box score |
| Oct 1, 1921 | Wabash 9, Purdue 0upset | Box score |
| Oct 1, 1921 | Washington 24, 9th Amry Corps 7 | Box score |
| Oct 1, 1921 | Washington and Lee 41, Randolph Macon 0 | Box score |
| Oct 1, 1921 | Washington St. Louis 10, Missouri–Rolla 0 | Box score |
| Oct 1, 1921 | West Virginia 50, Cincinnati 0 | Box score |
| Oct 1, 1921 | Wisconsin 28, Lawrence 0 | Box score |
| Oct 1, 1921 | Wofford 22, North Georgia 0 | Box score |
| Oct 1, 1921 | Yale 14, Vermont 0 | Box score |