| 1A Playoffs |
| 1st Round |
| 11/12/2021 (Fri) | | Tupelo Christian Prep 45-0 West Tallahatchie | | |
| 11/12/2021 (Fri) | | McEvans 32-0 Smithville | | |
| 11/12/2021 (Fri) | | Simmons 66-0 Okolona | | |
| 11/12/2021 (Fri) | | Biggersville 28-24 South Delta | | |
| 11/12/2021 (Fri) | | West Lowndes 40-6 Richton | | |
| 11/12/2021 (Fri) | | Taylorsville 31-13 French Camp Academy | | |
| 11/12/2021 (Fri) | | Bay Springs 48-0 Ethel | | |
| 11/12/2021 (Fri) | | Lumberton 40-39 Sebastopol | | |
| 2nd Round |
| 11/19/2021 (Fri) | | Tupelo Christian Prep 40-24 McEvans | | |
| 11/19/2021 (Fri) | | Simmons 66-30 Biggersville | | |
| 11/19/2021 (Fri) | | West Lowndes 36-21 Taylorsville | | |
| 11/19/2021 (Fri) | | Bay Springs 44-0 Lumberton | | |
| Semi-finals |
| 11/26/2021 (Fri) | | Simmons 48-0 Tupelo Christian Prep | | |
| 11/26/2021 (Fri) | | Bay Springs 44-6 West Lowndes | | |
| Championship Game |
| 12/3/2021 (Fri) | | Bay Springs 32-12 Simmons | | |
| 2A Playoffs |
| 1st Round |
| 11/5/2021 (Fri) | | Velma Jackson 48-0 East Marion | | |
| 11/5/2021 (Fri) | | Scott Central 54-8 Amite County | | |
| 11/5/2021 (Fri) | | Lake 49-6 Stringer | | |
| 11/5/2021 (Fri) | | East Union 43-7 OBannon | | |
| 11/5/2021 (Fri) | | East Webster 47-0 Coahoma County | | |
| 11/5/2021 (Fri) | | Leflore County 36-0 Potts Camp | | |
| 11/5/2021 (Fri) | | Northside 22-20 Calhoun City | 2OT | |
| 11/5/2021 (Fri) | | Charleston 46-18 Eupora | | |
| 11/5/2021 (Fri) | | George 44-22 Belmont | | |
| 11/5/2021 (Fri) | | Choctaw County 41-20 Palmer | | |
| 11/5/2021 (Fri) | | Baldwyn 41-12 Leland | | |
| 11/5/2021 (Fri) | | Kemper County 47-14 Collins | | |
| 11/5/2021 (Fri) | | Philadelphia 32-30 Heidelberg | | |
| 11/5/2021 (Fri) | | Newton 36-30 Mize | | |
| 11/5/2021 (Fri) | | Pelahatchie 44-23 Bogue Chitto | | |
| 11/5/2021 (Fri) | | Pisgah 31-20 Loyd Star | | |
| 2nd Round |
| 11/12/2021 (Fri) | | Kemper County 18-16 Velma Jackson | | |
| 11/12/2021 (Fri) | | Scott Central 54-25 Lake | | |
| 11/12/2021 (Fri) | | Leflore County 12-6 Northside | OT | |
| 11/12/2021 (Fri) | | Charleston 42-6 George | | |
| 11/12/2021 (Fri) | | Pelahatchie 39-35 Philadelphia | | |
| 11/12/2021 (Fri) | | Newton 48-14 Pisgah | | |
| 11/12/2021 (Fri) | | East Webster 34-31 East Union | | |
| 11/12/2021 (Fri) | | Baldwyn 30-14 Choctaw County | | |
| 3rd Round |
| 11/19/2021 (Fri) | | Pelahatchie 48-20 Kemper County | | |
| 11/19/2021 (Fri) | | Scott Central 60-14 Newton | | |
| 11/19/2021 (Fri) | | Leflore County 14-13 East Webster | | |
| 11/19/2021 (Fri) | | Charleston 28-10 Baldwyn | | |
| Semi-finals |
| 11/26/2021 (Fri) | | Scott Central 60-14 Pelahatchie | | |
| 11/26/2021 (Fri) | | Leflore County 24-22 Charleston | | |
| Championship Game |
| 12/4/2021 (Sat) | | Scott Central 72-24 Leflore County | | |
| 3A Playoffs |
| 1st Round |
| 11/5/2021 (Fri) | | Enterprise Clarke 42-7 Seminary | | |
| 11/5/2021 (Fri) | | Magee 47-6 Jefferson County | | |
| 11/5/2021 (Fri) | | Jefferson Davis County 54-19 Clarkdale | | |
| 11/5/2021 (Fri) | | Hazlehurst 42-8 Franklin County | | |
| 11/5/2021 (Fri) | | Tylertown 44-6 Wesson | | |
| 11/5/2021 (Fri) | | Union 28-14 West Marion | | |
| 11/5/2021 (Fri) | | Raleigh 43-0 Wilkinson County | | |
| 11/5/2021 (Fri) | | Morton 42-31 Saint Stanislaus | | |
| 11/5/2021 (Fri) | | Kossuth 32-7 Nettleton | | |
| 11/5/2021 (Fri) | | Yazoo County 40-20 Rosa Fort | | |
| 11/5/2021 (Fri) | | Amory 54-6 Mantachie | | |
| 11/5/2021 (Fri) | | Independence 24-20 Humphreys County | | |
| 11/5/2021 (Fri) | | Winona 52-0 Byhalia | | |
| 11/5/2021 (Fri) | | Noxubee County 24-7 Booneville | | |
| 11/5/2021 (Fri) | | North Panola 60-6 Thomas Edwards | | |
| 11/5/2021 (Fri) | | Aberdeen 12-9 Water Valley | | |
| 2nd Round |
| 11/5/2021 (Fri) | | Enterprise Clarke 21-14 Magee | | |
| 11/12/2021 (Fri) | | Jefferson Davis County 40-14 Hazlehurst | | |
| 11/12/2021 (Fri) | | Tylertown 20-8 Union | | |
| 11/12/2021 (Fri) | | Raleigh 43-27 Morton | | |
| 11/12/2021 (Fri) | | Kossuth 27-14 Yazoo County | | |
| 11/12/2021 (Fri) | | Amory 45-6 Independence | | |
| 11/12/2021 (Fri) | | Winona 36-8 Noxubee County | | |
| 11/12/2021 (Fri) | | North Panola 20-6 Aberdeen | | |
| 3rd Round |
| 11/19/2021 (Fri) | | Jefferson Davis County 34-7 Enterprise Clarke | | |
| 11/19/2021 (Fri) | | Raleigh 7-6 Tylertown | OT | |
| 11/19/2021 (Fri) | | Amory 14-0 Kossuth | | |
| 11/19/2021 (Fri) | | North Panola 52-20 Winona | | |
| Semi-finals |
| 11/26/2021 (Fri) | | Jefferson Davis County 26-20 Raleigh | | |
| 11/26/2021 (Fri) | | Amory 29-16 North Panola | | |
| Championship Game |
| 12/3/2021 (Fri) | | Jefferson Davis County 42-10 Amory | | |
| 4A Playoffs |
| 1st Round |
| 11/5/2021 (Fri) | | Poplarville 42-7 Raymond | | |
| 11/5/2021 (Fri) | | McComb 26-20 Lawrence County | | |
| 11/5/2021 (Fri) | | Moss Point 40-0 Northeast Jones | | |
| 11/5/2021 (Fri) | | Bay 39-33 Quitman | | |
| 11/5/2021 (Fri) | | Columbia 35-7 South Pike | | |
| 11/5/2021 (Fri) | | North Pike 37-27 Sumrall | | |
| 11/5/2021 (Fri) | | Newton County 3-0 Pass Christian | | |
| 11/5/2021 (Fri) | | Itawamba AHS 28-14 Choctaw Central | | |
| 11/5/2021 (Fri) | | Ripley 35-14 Yazoo City | | |
| 11/5/2021 (Fri) | | West Lauderdale 72-15 Mooreville | | |
| 11/5/2021 (Fri) | | Senatobia 48-30 Houston | | |
| 11/5/2021 (Fri) | | Clarksdale 40-0 South Pontotoc | | |
| 11/5/2021 (Fri) | | Louisville 37-12 Shannon | | |
| 11/5/2021 (Fri) | | Pontotoc 35-34 Gentry | 2OT | |
| 11/5/2021 (Fri) | | Caledonia 31-24 Kosciusko | | |
| 11/5/2021 (Fri) | | Mendenhall 29-15 Stone | | |
| 2nd Round |
| 11/12/2021 (Fri) | | Itawamba AHS 30-9 Ripley | | |
| 11/12/2021 (Fri) | | Columbia 48-21 Bay | | |
| 11/12/2021 (Fri) | | Mendenhall 21-20 McComb | | |
| 11/12/2021 (Fri) | | Newton County 38-20 North Pike | | |
| 11/12/2021 (Fri) | | Senatobia 27-22 West Lauderdale | | |
| 11/12/2021 (Fri) | | Poplarville 28-18 Moss Point | | |
| 11/12/2021 (Fri) | | Louisville 16-12 Clarksdale | | |
| 11/12/2021 (Fri) | | Caledonia 27-8 Pontotoc | | |
| 3rd Round |
| 11/19/2021 (Fri) | | Poplarville 21-12 Mendenhall | | |
| 11/19/2021 (Fri) | | Senatobia 45-6 Itawamba AHS | | |
| 11/19/2021 (Fri) | | Columbia 41-25 Newton County | | |
| 11/19/2021 (Fri) | | Caledonia 27-7 Louisville | | |
| Semi-finals |
| 11/26/2021 (Fri) | | Columbia 12-7 Poplarville | | |
| 11/26/2021 (Fri) | | Senatobia 34-27 Caledonia | | |
| Championship Game |
| 12/4/2021 (Sat) | | Columbia 22-21 Senatobia | | |
| 5A Playoffs |
| 1st Round |
| 11/12/2021 (Fri) | | West Point 40-7 Ridgeland | | |
| 11/12/2021 (Fri) | | Vicksburg 25-3 Cleveland Central | | |
| 11/12/2021 (Fri) | | Neshoba Central 27-24 Lake Cormorant | | |
| 11/12/2021 (Fri) | | Lafayette 43-16 Holmes County Central | | |
| 11/12/2021 (Fri) | | West Jones 31-28 Gautier | | |
| 11/12/2021 (Fri) | | Laurel 59-20 George County | | |
| 11/12/2021 (Fri) | | Picayune 35-13 Hattiesburg | | |
| 11/12/2021 (Fri) | | Brookhaven 42-14 East Central | | |
| 2nd Round |
| 11/19/2021 (Fri) | | West Point 42-6 Vicksburg | | |
| 11/19/2021 (Fri) | | Neshoba Central 23-20 Lafayette | | |
| 11/19/2021 (Fri) | | Laurel 30-20 West Jones | | |
| 11/19/2021 (Fri) | | Picayune 28-3 Brookhaven | | |
| Semi-finals |
| 11/26/2021 (Fri) | | West Point 20-14 Neshoba Central | | |
| 11/26/2021 (Fri) | | Picayune 32-28 Laurel | | |
| Championship Game |
| 12/4/2021 (Sat) | | Picayune 40-21 West Point | | |
| 6A Playoffs |
| 1st Round |
| 11/12/2021 (Fri) | | Oxford 35-28 South Panola | | |
| 11/12/2021 (Fri) | | Madison Central 42-7 DeSoto Central | | |
| 11/12/2021 (Fri) | | Starkville 63-21 Hernando | | |
| 11/12/2021 (Fri) | | Southaven 14-10 Clinton | | |
| 11/12/2021 (Fri) | | Brandon 39-13 Harrison Central | | |
| 11/12/2021 (Fri) | | Warren Central 30-21 DIberville | | |
| 11/12/2021 (Fri) | | Ocean Springs 54-28 Pearl | | |
| 11/12/2021 (Fri) | | Oak Grove 33-7 Gulfport | | |
| 2nd Round |
| 11/19/2021 (Fri) | | Madison Central 31-21 Oxford | | |
| 11/19/2021 (Fri) | | Starkville 42-27 Southaven | | |
| 11/19/2021 (Fri) | | Brandon 42-17 Warren Central | | |
| 11/19/2021 (Fri) | | Oak Grove 28-21 Ocean Springs | | |
| Semi-finals |
| 11/26/2021 (Fri) | | Madison Central 34-13 Starkville | | |
| 11/26/2021 (Fri) | | Brandon 21-20 Oak Grove | | |
| Championship Game |
| 12/3/2021 (Fri) | | Madison Central 24-17 Brandon | | |
| MAIS-1A Playoffs |
| 1st Round |
| 10/29/2021 (Fri) | | Lee Academy AR 54-26 Franklin Academy TN | | |
| 10/29/2021 (Fri) | | Sharkey-Issaquena Academy 58-0 Northeast Baptist LA | | |
| 10/29/2021 (Fri) | | Tensas Academy LA 34-32 Deer Creek | | |
| 10/29/2021 (Fri) | | Delta Academy 64-22 Union Christian LA | | |
| 2nd Round |
| 11/5/2021 (Fri) | | DeSoto Academy AR 42-0 Lee Academy AR | | |
| 11/5/2021 (Fri) | | Wilkinson Christian 44-6 Sharkey-Issaquena Academy | | |
| 11/5/2021 (Fri) | | Riverdale Academy LA 58-24 Tensas Academy LA | | |
| 11/5/2021 (Fri) | | Briarfield Academy LA 52-12 Delta Academy | | |
| Semi-finals |
| 11/12/2021 (Fri) | | DeSoto Academy AR 44-38 Wilkinson Christian | | |
| 11/12/2021 (Fri) | | Briarfield Academy LA 6-0 Riverdale Academy LA | | |
| MAIS-2A Playoffs |
| 1st Round |
| 10/29/2021 (Fri) | | Tallulah Academy LA 44-36 Porters Chapel Academy | | |
| 10/29/2021 (Fri) | | Calhoun Academy 42-14 Tunica Academy | | |
| 10/29/2021 (Fri) | | Humphreys Academy 44-16 Marvell Academy AR | | |
| 10/29/2021 (Fri) | | North Sunflower Academy 62-14 Christian Collegiate Academy | | |
| 2nd Round |
| 11/5/2021 (Fri) | | Manchester Academy 44-40 Tallulah Academy LA | | |
| 11/5/2021 (Fri) | | Claiborne Academy LA 50-8 Calhoun Academy | | |
| 11/5/2021 (Fri) | | Prairie View Academy LA 51-14 Humphreys Academy | | |
| 11/5/2021 (Fri) | | North Sunflower Academy 60-32 Newton County Academy | | |
| Semi-finals |
| 11/12/2021 (Fri) | | Manchester Academy 42-36 Claiborne Academy LA | | |
| 11/12/2021 (Fri) | | Prairie View Academy LA 24-12 North Sunflower Academy | | |
| Championship Game |
| 11/19/2021 (Fri) | | Prairie View Academy LA 50-27 Manchester Academy | | |
| MAIS-3A Playoffs |
| 1st Round |
| 10/29/2021 (Fri) | | Winina Christian 49-14 Delta Streets Academy | | |
| 10/29/2021 (Fri) | | Amite 58-21 Rossville TN | | |
| 10/29/2021 (Fri) | | Sylva Bay Academy 35-14 Hillcrest Christian | | |
| 2nd Round |
| 11/5/2021 (Fri) | | Greenville Christian 50-0 Winina Christian | | |
| 11/5/2021 (Fri) | | Central Holmes Christian 42-28 Benton Academy | | |
| 11/5/2021 (Fri) | | Centreville Academy 36-14 Amite | | |
| 11/5/2021 (Fri) | | Canton Academy 40-28 Sylva Bay Academy | | |
| Semi-finals |
| 11/19/2021 (Fri) | | Greenville Christian 52-6 Central Holmes Christian | | |
| 11/19/2021 (Fri) | | Canton Academy 35-18 Centreville Academy | | |
| Championship Game |
| 11/18/2021 (Thu) | | Greenville Christian 46-6 Canton Academy | | |
| MAIS-4A Playoffs |
| 1st Round |
| 10/29/2021 (Fri) | | Indianola Academy 27-15 Carroll Academy | | |
| 10/29/2021 (Fri) | | Tri-County Academy 50-12 Columbia Academy | | |
| 10/29/2021 (Fri) | | Riverfield LA 28-8 Winston Academy | | |
| 10/29/2021 (Fri) | | Kirk Academy 7-6 Marshall Academy | | |
| 2nd Round |
| 11/5/2021 (Fri) | | Saint Joseph Greenville 41-20 Indianola Academy | | |
| 11/5/2021 (Fri) | | Tri-County Academy 56-14 Oak Hill Academy | | |
| 11/5/2021 (Fri) | | Adams Christian 41-7 Riverfield LA | | |
| 11/5/2021 (Fri) | | Kirk Academy 45-38 Brookhaven Academy | | |
| Semi-finals |
| 11/12/2021 (Fri) | | Tri-County Academy 14-7 Saint Joseph Greenville | | |
| 11/12/2021 (Fri) | | Kirk Academy 16-7 Adams Christian | | |
| Championship Game |
| 11/19/2021 (Fri) | | Tri-County Academy 44-22 Kirk Academy | | |
| MAIS-5A Playoffs |
| 1st Round |
| 10/29/2021 (Fri) | | Pillow Academy 34-30 Central Hinds Academy | | |
| 10/29/2021 (Fri) | | Bayou Academy 34-6 Cathedral | | |
| 10/29/2021 (Fri) | | Starkville Academy 17-7 Lamar | | |
| 10/29/2021 (Fri) | | Simpson Academy 41-13 Saint Joseph Madison | | |
| 2nd Round |
| 11/5/2021 (Fri) | | Leake Academy 49-14 Pillow Academy | | |
| 11/5/2021 (Fri) | | Copiah Academy 26-21 Bayou Academy | | |
| 11/5/2021 (Fri) | | Heritage Academy 31-12 Starkville Academy | | |
| 11/5/2021 (Fri) | | Oak Forest LA 30-22 Simpson Academy | | |
| Semi-finals |
| 11/12/2021 (Fri) | | Copiah Academy 33-21 Leake Academy | | |
| 11/12/2021 (Fri) | | Heritage Academy 28-21 Oak Forest LA | | |
| Championship Game |
| 11/19/2021 (Fri) | | Heritage Academy 51-21 Copiah Academy | | |
| MAIS-6A Playoffs |
| 1st Round |
| 11/5/2021 (Fri) | | Jackson Academy 40-15 Presbyterian Christian | | |
| 11/5/2021 (Fri) | | Jackson Prep 55-13 Parklane Academy | | |
| Semi-finals |
| 11/12/2021 (Fri) | | Madison-Ridgeland Academy 52-14 Jackson Academ | | |
| 11/12/2021 (Fri) | | Hartfield Academy 17-13 Jackson Prep | | |
