Southern Arkansas was voted the No. 1 team in the 2021 NFCA Division II Top 25 Preseason Coaches Poll. The Muleriders collected all 16 first-place votes to start the season atop the rankings. SAU finished the pandemic shortened 2020 season ranked No. 1 and on a 16-game winning streak.
| 1 | Southern Arkansas (16) | 400 | 22-2 | 1 |
| 2 | North Georgia | 381 | 23-4 | 3 |
| 3 | Augustana | 358 | 16-3 | 4 |
| 4 | UT Tyler | 354 | 17-3 | 5 |
| 5 | Angelo State | 318 | 19-6 | 7 |
| 6 | Young Harris | 314 | 19-3 | 6 |
| 7 | Saint Leo | 312 | 23-7 | 8 |
| 8 | Rollins | 280 | 21-3 | 9 |
| 9 | Texas A&M-Commerce | 260 | 16-7 | 10 |
| 10 | Trevecca Nazarene | 258 | 15-3 | 11 |
| 11 | Concordia Irvine | 238 | 17-5 | 13 |
| 12 | Valdosta State | 196 | 18-5 | 15 |
| 13 | Oklahoma Christian | 179 | 21-5 | 16 |
| 14 | Saint Anselm | 168 | 16-4 | 12 |
| 15 | Winona State | 166 | 13-7 | NR |
| 16 | Lenoir-Rhyne | 164 | 20-4 | 21 |
| 17 | Southern Indiana | 141 | 15-4 | 19 |
| 18 | Rogers State | 136 | 21-8 | 17 |
| 19 | Lubbock Christian | 109 | 20-6 | 18 |
| 20 | UAH | 101 | 15-8 | 25 |
| 21 | Indianapolis | 86 | 14-5 | RV |
| 22 | Lincoln Memorial | 83 | 16-5 | 14 |
| 23 | West Chester | 66 | 12-3 | NR |
| 24 | Tampa | 38 | 19-9 | RV |
| 25 | Grand Valley State | 23 | 13-3 | RV |
Receiving Votes: Minnesota State (18), West Liberty (18), Francis Marion (9), Metropolitan State University of Denver (9), Biola (8), St. Cloud State (5), Central Oklahoma (2), Texas A&M University-Kingsville (2).