| Oct 14, 2021 | Southern Nazarene 30, Southwestern Oklahoma State 22 | Box score |
| Oct 15, 2021 | Cornell 34, Colgate 20 | Box score |
| Oct 15, 2021 | Montana State 13, Weber State 7 | Box score |
| Oct 16, 2021 | UConn 21, Yale 15 | Box score |
| Oct 16, 2021 | Maine 27, William & Mary 16 | Box score |
| Oct 16, 2021 | Marist 20, Dayton 17upset | Box score |
| Oct 16, 2021 | Incarnate Word 38, Nicholls 21 | Box score |
| Oct 16, 2021 | Wayne State (MI) 16, Davenport 3upset | Box score |
| Oct 16, 2021 | New Haven 30, American International 14 | Box score |
| Oct 16, 2021 | Michigan Tech 21, Northern Michigan 14 | Box score |
| Oct 16, 2021 | Merrimack 43, Long Island University 5 | Box score |
| Oct 16, 2021 | West Chester 42, East Stroudsburg 24 | Box score |
| Oct 16, 2021 | Mercyhurst 27, Edinboro 20upset | Box score |
| Oct 16, 2021 | Findlay 21, Ohio Dominican 14 | Box score |
| Oct 16, 2021 | Bryant 18, Saint Francis 17 | Box score |
| Oct 16, 2021 | Charleston (WV) 48, Concord 3 | Box score |
| Oct 16, 2021 | Princeton 56, Brown 42 | Box score |
| Oct 16, 2021 | Bowie State 51, Virginia State 44 | Box score |
| Oct 16, 2021 | Lincoln (PA) 17, Elizabeth City State 14 | Box score |
| Oct 16, 2021 | Virginia Union 38, Chowan 31 | Box score |
| Oct 16, 2021 | Monmouth 34, Campbell 17 | Box score |
| Oct 16, 2021 | Dartmouth 38, New Hampshire 21 | Box score |
| Oct 16, 2021 | Shaw 20, Livingstone 9 | Box score |
| Oct 16, 2021 | South Dakota State 41, Western Illinois 17 | Box score |
| Oct 16, 2021 | Prairie View A&M 35, Bethune-Cookman 29 | Box score |
| Oct 16, 2021 | Tiffin 27, Ashland 21 | Box score |
| Oct 16, 2021 | Mississippi College 20, Shorter 7 | Box score |
| Oct 16, 2021 | Tuskegee 29, Central State 0 | Box score |
| Oct 16, 2021 | IU Pennsylvania 48, Slippery Rock 21upset | Box score |
| Oct 16, 2021 | Glenville State 35, Alderson-Broaddus 21 | Box score |
| Oct 16, 2021 | Notre Dame College 52, West Virginia Wesleyan 14 | Box score |
| Oct 16, 2021 | Lake Erie 33, Hillsdale 14upset | Box score |
| Oct 16, 2021 | Minnesota State 58, Upper Iowa 0 | Box score |
| Oct 16, 2021 | Lenoir Rhyne 59, Carson Newman 0 | Box score |
| Oct 16, 2021 | Stonehill 31, Saint Anselm 22 | Box score |
| Oct 16, 2021 | Sacred Heart 27, Central Connecticut 17 | Box score |
| Oct 16, 2021 | St. Thomas (MN) 38, Stetson 7upset | Box score |
| Oct 16, 2021 | Kentucky State 76, Edward Waters 36 | Box score |
| Oct 16, 2021 | Kentucky Wesleyan 23, Walsh 13 | Box score |
| Oct 16, 2021 | Pace 39, Franklin Pierce 31 | Box score |
| Oct 16, 2021 | Harvard 30, Lafayette 3 | Box score |
| Oct 16, 2021 | Fordham 66, Bucknell 21 | Box score |
| Oct 16, 2021 | West Liberty 52, Fairmont State 31 | Box score |
| Oct 16, 2021 | Minnesota Duluth 33, Concordia St. Paul 13 | Box score |
| Oct 16, 2021 | Winston-Salem State 41, St. Augustine’s 0 | Box score |
| Oct 16, 2021 | Columbia 23, Pennsylvania 14 | Box score |
| Oct 16, 2021 | Holy Cross 48, Georgetown 14 | Box score |
| Oct 16, 2021 | Chattanooga 21, East Tennessee State 16 | Box score |
| Oct 16, 2021 | Samford 27, Wofford 24 | Box score |
| Oct 16, 2021 | Tusculum 37, UVA Wise 21 | Box score |
| Oct 16, 2021 | Fayetteville State 55, Johnson C. Smith 12 | Box score |
| Oct 16, 2021 | James Madison 19, Richmond 3 | Box score |
| Oct 16, 2021 | Norfolk State 42, Virginia Lynchburg 14 | Box score |
| Oct 16, 2021 | Florida A&M 35, Alabama A&M 31 | Box score |
| Oct 16, 2021 | Missouri S&T 37, William Jewell 16 | Box score |
| Oct 16, 2021 | Southwest Baptist 27, Truman State 21upset | Box score |
| Oct 16, 2021 | Saginaw Valley State 31, Northwood 13 | Box score |
| Oct 16, 2021 | Valdosta State 42, West Alabama 17 | Box score |
| Oct 16, 2021 | Bemidji State 22, Minnesota St Moorhead 19 | Box score |
| Oct 16, 2021 | Winona State 26, Southwest Minnesota State 14 | Box score |
| Oct 16, 2021 | Albany State 28, Benedict 6 | Box score |
| Oct 16, 2021 | Morehouse 51, Fort Valley State 3upset | Box score |
| Oct 16, 2021 | Sioux Falls 34, University of Mary 14 | Box score |
| Oct 16, 2021 | Augustana (SD) 32, Wayne State (NE) 24 | Box score |
| Oct 16, 2021 | Bloomsburg 44, Lock Haven 0 | Box score |
| Oct 16, 2021 | Colorado Mesa 55, Fort Lewis 3 | Box score |
| Oct 16, 2021 | Colorado School of Mines 44, South Dakota Mines 24 | Box score |
| Oct 16, 2021 | Shepherd 38, Millersville 13 | Box score |
| Oct 16, 2021 | Nebraska Kearney 42, Emporia State 35 | Box score |
| Oct 16, 2021 | Pittsburg State 59, Lincoln (MO) 7 | Box score |
| Oct 16, 2021 | Washburn 17, Northwest Missouri State 16 | Box score |
| Oct 16, 2021 | Frostburg State 41, Wheeling 17 | Box score |
| Oct 16, 2021 | Bentley 34, Southern Connecticut State 20 | Box score |
| Oct 16, 2021 | Eastern Washington 71, Idaho 21 | Box score |
| Oct 16, 2021 | Sacramento State 28, Montana 21upset | Box score |
| Oct 16, 2021 | Southern Arkansas 34, Arkansas Tech 17 | Box score |
| Oct 16, 2021 | Ouachita Baptist 34, Arkansas Monticello 0 | Box score |
| Oct 16, 2021 | North Dakota State 20, Illinois State 0 | Box score |
| Oct 16, 2021 | Missouri State 37, Indiana State 7 | Box score |
| Oct 16, 2021 | Southern Illinois 31, North Dakota 28 | Box score |
| Oct 16, 2021 | Harding 46, Henderson State 21 | Box score |
| Oct 16, 2021 | UT Martin 28, Eastern Illinois 17 | Box score |
| Oct 16, 2021 | Murray State 32, Southeast Missouri State 31 | Box score |
| Oct 16, 2021 | Tennessee State 20, Tennessee Tech 13 | Box score |
| Oct 16, 2021 | Southeastern Oklahoma State 43, Northwestern (OK) 10 | Box score |
| Oct 16, 2021 | Morehead State 31, Butler 8 | Box score |
| Oct 16, 2021 | Jackson State 28, Alabama State 7 | Box score |
| Oct 16, 2021 | Southern 34, Arkansas–Pine Bluff 7 | Box score |
| Oct 16, 2021 | Grambling 34, Texas Southern 20 | Box score |
| Oct 16, 2021 | Savannah State 49, Clark Atlanta 14 | Box score |
| Oct 16, 2021 | Miles 34, Lane College 31 | Box score |
| Oct 16, 2021 | North Greenville 42, Delta State 34upset | Box score |
| Oct 16, 2021 | Chadron State 45, Adams State 35 | Box score |
| Oct 16, 2021 | Western Colorado 44, Black Hills State 28 | Box score |
| Oct 16, 2021 | New Mexico Highlands 28, CSU Pueblo 21upset | Box score |
| Oct 16, 2021 | Simon Fraser 30, MONTANASTN 3upset | Box score |
| Oct 16, 2021 | Villanova 17, UAlbany 10 | Box score |
| Oct 16, 2021 | Stony Brook 34, Delaware 17upset | Box score |
| Oct 16, 2021 | South Carolina State 37, Morgan State 14 | Box score |
| Oct 16, 2021 | Abilene Christian 24, Lamar 17 | Box score |
| Oct 16, 2021 | Northern Arizona 59, Southern Utah 35 | Box score |
| Oct 16, 2021 | Towson 28, Rhode Island 7 | Box score |
| Oct 16, 2021 | VMI 45, Mercer 7 | Box score |
| Oct 16, 2021 | McNeese 35, Northwestern State 17 | Box score |
| Oct 16, 2021 | Alcorn State 24, Mississippi Valley State 12 | Box score |
| Oct 16, 2021 | McKendree 51, Quincy 48 | Box score |
| Oct 16, 2021 | Gannon 14, Seton Hill 10 | Box score |
| Oct 16, 2021 | Mars Hill 32, Limestone 3 | Box score |
| Oct 16, 2021 | Erskine 24, Bluefield State 19upset | Box score |
| Oct 16, 2021 | Eastern Kentucky 38, Central Arkansas 35 | Box score |
| Oct 16, 2021 | Portland State 31, Idaho State 10 | Box score |
| Oct 16, 2021 | Kennesaw State 14, North Carolina A&T 0 | Box score |
| Oct 16, 2021 | South Dakota 34, Northern Iowa 21 | Box score |
| Oct 16, 2021 | SE Louisiana 61, Houston Christian 24 | Box score |
| Oct 16, 2021 | West Georgia 30, West Florida 26 | Box score |
| Oct 16, 2021 | East Texas A&M 58, Western New Mexico 0 | Box score |
| Oct 16, 2021 | Missouri Southern State 30, Central Missouri 28 | Box score |
| Oct 16, 2021 | Missouri Western 57, Northeastern State 24 | Box score |
| Oct 16, 2021 | Newberry 14, Catawba 7 | Box score |
| Oct 16, 2021 | San Diego 13, Drake 10 | Box score |
| Oct 16, 2021 | Kutztown 20, Shippensburg 3 | Box score |
| Oct 16, 2021 | Charleston Southern 35, Hampton 5 | Box score |
| Oct 16, 2021 | Furman 24, The Citadel 14 | Box score |
| Oct 16, 2021 | Lindenwood 28, Indianapolis 20 | Box score |
| Oct 16, 2021 | Barton 26, Wingate 20 | Box score |
| Oct 16, 2021 | UNC Pembroke 14, West Virginia State 13 | Box score |
| Oct 16, 2021 | North Alabama 42, Robert Morris 31 | Box score |
| Oct 16, 2021 | Oklahoma Baptist 47, East Central 20 | Box score |
| Oct 16, 2021 | Ferris State 35, Grand Valley State 28 | Box score |
| Oct 16, 2021 | Northern State 36, Minot State 35 | Box score |
| Oct 16, 2021 | Angelo State 34, UT Permian Basin 14 | Box score |
| Oct 16, 2021 | Davidson 70, Presbyterian 35 | Box score |
| Oct 16, 2021 | UC Davis 32, Northern Colorado 3 | Box score |
| Oct 16, 2021 | Central Oklahoma 24, Fort Hays 14 | Box score |
| Oct 16, 2021 | West Texas 44, Eastern New Mexico 24 | Box score |
| Oct 16, 2021 | Texas A&M–Kingsville 51, Lincoln (CA) 21 | Box score |
| Oct 16, 2021 | Tarleton State 41, Utah Tech 20 | Box score |