| Nov 18, 2021 | Nicholls 45, SE Louisiana 42upset | Box score |
| Nov 20, 2021 | 1Georgia 56, Charleston Southern 7 | Box score |
| Nov 20, 2021 | Mississippi State 55, Tennessee State 10 | Box score |
| Nov 20, 2021 | 16Texas A&M 52, Prairie View A&M 3 | Box score |
| Nov 20, 2021 | North Carolina 34, Wofford 14 | Box score |
| Nov 20, 2021 | Robert Morris 20, Campbell 17 | Box score |
| Nov 20, 2021 | Dartmouth 52, Brown 31 | Box score |
| Nov 20, 2021 | Morgan State 28, Georgetown 21 | Box score |
| Nov 20, 2021 | Colgate 45, Fordham 31 | Box score |
| Nov 20, 2021 | Butler 28, Marist 21upset | Box score |
| Nov 20, 2021 | Duquesne 44, Wagner 0 | Box score |
| Nov 20, 2021 | Sacred Heart 38, Long Island University 14 | Box score |
| Nov 20, 2021 | Central Connecticut 24, Saint Francis 21 | Box score |
| Nov 20, 2021 | Lehigh 17, Lafayette 10 | Box score |
| Nov 20, 2021 | Harvard 34, Yale 31 | Box score |
| Nov 20, 2021 | Shepherd 38, Findlay 31 | Box score |
| Nov 20, 2021 | Notre Dame College 33, Slippery Rock 25 | Box score |
| Nov 20, 2021 | Western Carolina 52, VMI 24upset | Box score |
| Nov 20, 2021 | Gardner-Webb 35, North Carolina A&T 27upset | Box score |
| Nov 20, 2021 | North Alabama 35, Hampton 27upset | Box score |
| Nov 20, 2021 | Kennesaw State 49, Monmouth 17 | Box score |
| Nov 20, 2021 | Stony Brook 36, UAlbany 14 | Box score |
| Nov 20, 2021 | Villanova 21, Delaware 13 | Box score |
| Nov 20, 2021 | Maine 33, New Hampshire 20 | Box score |
| Nov 20, 2021 | Columbia 34, Cornell 26 | Box score |
| Nov 20, 2021 | Princeton 34, Pennsylvania 14 | Box score |
| Nov 20, 2021 | Indiana State 15, Illinois State 10upset | Box score |
| Nov 20, 2021 | Youngstown State 35, Southern Illinois 18upset | Box score |
| Nov 20, 2021 | Murray State 20, Eastern Illinois 13 | Box score |
| Nov 20, 2021 | Holy Cross 45, Bucknell 6 | Box score |
| Nov 20, 2021 | Furman 41, Samford 34 | Box score |
| Nov 20, 2021 | Northwestern State 24, McNeese 20upset | Box score |
| Nov 20, 2021 | East Tennessee State 38, Mercer 35 | Box score |
| Nov 20, 2021 | Bryant 58, Merrimack 14 | Box score |
| Nov 20, 2021 | Davidson 45, Drake 14 | Box score |
| Nov 20, 2021 | San Diego 41, Stetson 16 | Box score |
| Nov 20, 2021 | Howard 56, Virginia Lynchburg 6 | Box score |
| Nov 20, 2021 | Grand Valley State 20, Lindenwood 3 | Box score |
| Nov 20, 2021 | Bemidji State 28, Augustana (SD) 24 | Box score |
| Nov 20, 2021 | New Haven 38, Bentley 13 | Box score |
| Nov 20, 2021 | West Georgia 23, Albany State 7upset | Box score |
| Nov 20, 2021 | Bowie State 31, Lenoir Rhyne 10 | Box score |
| Nov 20, 2021 | Newberry 33, West Florida 30upset | Box score |
| Nov 20, 2021 | The Citadel 24, Chattanooga 21upset | Box score |
| Nov 20, 2021 | Eastern Kentucky 39, Jacksonville State 31 | Box score |
| Nov 20, 2021 | Sam Houston 35, Abilene Christian 9 | Box score |
| Nov 20, 2021 | Montana 29, Montana State 10 | Box score |
| Nov 20, 2021 | Elon 43, Rhode Island 28 | Box score |
| Nov 20, 2021 | James Madison 56, Towson 10 | Box score |
| Nov 20, 2021 | North Carolina Central 34, Delaware State 28 | Box score |
| Nov 20, 2021 | South Carolina State 31, Norfolk State 21 | Box score |
| Nov 20, 2021 | Northern Iowa 41, Western Illinois 3 | Box score |
| Nov 20, 2021 | Morehead State 51, Valparaiso 38 | Box score |
| Nov 20, 2021 | Jackson State 24, Alcorn State 10 | Box score |
| Nov 20, 2021 | Alabama A&M 52, Arkansas–Pine Bluff 24 | Box score |
| Nov 20, 2021 | New Mexico Highlands 31, Western New Mexico 28 | Box score |
| Nov 20, 2021 | Southeast Missouri State 31, UT Martin 14upset | Box score |
| Nov 20, 2021 | St. Thomas (MN) 54, Presbyterian 15 | Box score |
| Nov 20, 2021 | Harding 30, Washburn 14 | Box score |
| Nov 20, 2021 | Angelo State 48, Minnesota Duluth 14 | Box score |
| Nov 20, 2021 | Northwest Missouri State 50, Central Washington 21 | Box score |
| Nov 20, 2021 | Idaho 14, Idaho State 0 | Box score |
| Nov 20, 2021 | Weber State 48, Northern Colorado 17 | Box score |
| Nov 20, 2021 | South Dakota State 24, North Dakota 21 | Box score |
| Nov 20, 2021 | Austin Peay 48, Tennessee Tech 20 | Box score |
| Nov 20, 2021 | Incarnate Word 55, Houston Christian 14 | Box score |
| Nov 20, 2021 | Alabama State 24, Texas Southern 21 | Box score |
| Nov 20, 2021 | Nebraska Kearney 31, Western Colorado 24 | Box score |
| Nov 20, 2021 | Richmond 20, William & Mary 17 | Box score |
| Nov 20, 2021 | North Dakota State 52, South Dakota 24 | Box score |
| Nov 20, 2021 | Florida A&M 46, Bethune-Cookman 21 | Box score |
| Nov 20, 2021 | Sacramento State 27, UC Davis 7 | Box score |
| Nov 20, 2021 | Stephen F. Austin 42, Lamar 6 | Box score |
| Nov 20, 2021 | Eastern Washington 42, Portland State 28 | Box score |
| Nov 20, 2021 | Tarleton State 24, Central Arkansas 3 | Box score |
| Nov 20, 2021 | Northern Arizona 45, Cal Poly 21 | Box score |
| Nov 20, 2021 | Missouri State 55, Utah Tech 24 | Box score |