| Thursday, September 8, 2022 |
| Harlan County | 45 | at Knox Central | 18 | | ⇄ |
| Newport Central Catholic | 40 | at Walton-Verona | 21 | | ⇄ |
| Friday, September 9, 2022 |
| Warren East | 60 | at Russellville | 12 | Linton-Wren Kick-off Classic | ⇄ |
| Woodward (Cincinnati), OH | 38 | at Bourbon County | 22 | Mingua Beef Jerky Bowl | |
| Estill County | 21 | vs. Dayton | 8 | Robbie Wiseman Memorial Classic | ⇄ |
| Mercer County | 17 | vs. Danville | 14 | Whitaker Bank Game | ⇄ |
| Adair County | 56 | at Clinton County | 6 | | ⇄ |
| Anderson County | 54 | at Breckinridge County | 30 | | ⇄ |
| Atherton | 56 | vs. Thomas Nelson | 7 | | ⇄ |
| Ballard | 44 | vs. Franklin County | 8 | | ⇄ |
| Bardstown | 21 | vs. Elizabethtown | 0 | | ⇄ |
| Barren County | 39 | vs. Monroe County | 6 | | ⇄ |
| Beechwood | 30 | vs. Simon Kenton | 7 | | ⇄ |
| Belfry | 24 | vs. Central | 21 | | ⇄ |
| Bell County | 40 | at Lincoln County | 30 | | ⇄ |
| Bethlehem | 49 | at Washington County | 13 | | ⇄ |
| Bishop Brossart | 11 | at Holy Cross (Covington) | 8 | | ⇄ |
| Bowling Green | 35 | at Hopkinsville | 6 | | ⇄ |
| Boyd County | 29 | at Greenup County | 21 | | ⇄ |
| Boyle County | 31 | vs. Henderson County | 17 | | ⇄ |
| Bracken County | 44 | at Trimble County | 8 | | ⇄ |
| Bullitt Central | 21 | at North Bullitt | 20 | | ⇄ |
| Bullitt East
| 54 | at Graves County | 21 | | ⇄ |
| Butler | 20 | at Fern Creek | 13 | | ⇄ |
| Butler County | 35 | vs. Grayson County | 13 | | ⇄ |
| Campbellsville | 30 | at Hart County | 21 | | ⇄ |
| Carroll County | 49 | vs. Grant County | 12 | | ⇄ |
| Casey County | 40 | at Russell County | 35 | | ⇄ |
| Central Hardin | 50 | vs. John Hardin | 0 | | ⇄ |
| Christian Academy-Louisville | 49 | at Lexington Christian | 14 | | ⇄ |
| Clay County | 47 | vs. Pike County Central | 0 | | ⇄ |
| Conner | 21 | vs. Scott | 20 | | ⇄ |
| Cooper | 28 | at Campbell County | 26 | | ⇄ |
| Corbin | 24 | vs. Pulaski County | 21 | | ⇄ |
| Covington Catholic | 47 | at Dixie Heights | 14 | | ⇄ |
| Crittenden County | 21 | at Caldwell County | 13 | | ⇄ |
| DuPont Manual | 47 | vs. Valley | 0 | | ⇄ |
| East Carter | 44 | at West Carter | 8 | | ⇄ |
| Fairdale | 41 | at Shelby County | 6 | | ⇄ |
| Fairview | 36 | vs. Morgan County | 8 | | ⇄ |
| Frankfort | 81 | vs. Doss | 60 | | ⇄ |
| Frederick Douglass | 54 | vs. Paul Laurence Dunbar | 7 | | ⇄ |
| Fulton County | 58 | vs. Ballard Memorial | 30 | | ⇄ |
| George Rogers Clark | 67 | vs. Montgomery County | 17 | | ⇄ |
| Gibson Southern (Fort Branch), IN | 28 | vs. South Warren | 24 | | |
| Glasgow | 28 | vs. Allen County-Scottsville | 7 | | ⇄ |
| Great Crossing | 37 | at East Jessamine | 7 | | ⇄ |
| Greenwood | 49 | vs. Warren Central | 8 | | ⇄ |
| Hancock County | 50 | vs. Edmonson County | 0 | | ⇄ |
| Hazard | 52 | vs. Letcher County Central | 50 | | ⇄ |
| Henry Clay | 18 | vs. Eastern | 12 | | ⇄ |
| Henry County | 48 | at Pendleton County | 6 | | ⇄ |
| Highlands | 24 | vs. Raceland | 14 | | ⇄ |
| Holmes | 32 | vs. Newport | 28 | | ⇄ |
| Holy Cross (Louisville) | 9 | at Western | 0 | | ⇄ |
| Hurley, VA | 42 | at Phelps | 12 | | |
| Kentucky Country Day | 49 | at Jeffersontown | 6 | | ⇄ |
| LaRue County | 44 | vs. Rockcastle County | 20 | | ⇄ |
| Lawrence County | 50 | at Russell | 10 | | ⇄ |
| Leslie County | 20 | at Floyd Central | 14 | | ⇄ |
| Lexington Catholic | 42 | vs. Pleasure Ridge Park | 19 | | ⇄ |
| Lloyd Memorial | 36 | vs. Boone County | 15 | | ⇄ |
| Logan County | 41 | at Franklin-Simpson | 31 | | ⇄ |
| Madison Central | 56 | at South Laurel | 6 | | ⇄ |
| Madison Southern | 37 | at Lafayette | 6 | | ⇄ |
| Madisonville-North Hopkins | 35 | vs. Christian County | 19 | | ⇄ |
| Magoffin County | 65 | vs. Bellevue | 20 | | ⇄ |
| Marshall County | 56 | vs. Calloway County | 14 | | ⇄ |
| Martin County | 41 | vs. Knott County Central | 0 | | ⇄ |
| Mayfield | 49 | at McCracken County | 26 | | ⇄ |
| McLean County | 43 | at Muhlenberg County | 14 | | ⇄ |
| Meade County | 36 | vs. Oldham County | 8 | | ⇄ |
| Metcalfe County | 46 | at Eminence | 0 | | ⇄ |
| Miami Valley Christian Academy (Cincinnati), OH | 36 | vs. Gallatin County | 18 | | |
| Middlesboro | 57 | at Lynn Camp | 0 | | ⇄ |
| Nelson County | 37 | at Marion County | 0 | | ⇄ |
| Nicholas County | 41 | vs. Fort Knox | 18 | | ⇄ |
| North Hardin | 52 | vs. Apollo | 25 | | ⇄ |
| North Laurel | 27 | vs. Shelby Valley | 12 | | ⇄ |
| Owensboro Catholic | 21 | vs. Owensboro | 17 | | ⇄ |
| Paris | 42 | vs. Ludlow | 8 | | ⇄ |
| Perry County Central | 28 | vs. Breathitt County | 26 | | ⇄ |
| Pineville | 44 | vs. McCreary Central | 6 | | ⇄ |
| Prestonsburg | 42 | at Powell County | 26 | | ⇄ |
| Rowan County | 21 | at Fleming County | 20 | | ⇄ |
| Ryle | 23 | vs. Daviess County | 7 | | ⇄ |
| Scott County | 21 | vs. Bryan Station | 20 | | ⇄ |
| Seneca | 34 | vs. Waggener | 6 | | ⇄ |
| Shawnee | 40 | vs. Jackson County | 0 | | ⇄ |
| Somerset | 35 | at Paintsville | 34 | (OT) | ⇄ |
| South Oldham | 41 | vs. North Oldham | 9 | | ⇄ |
| Southern | 15 | vs. Iroquois | 0 | | ⇄ |
| Spencer County | 43 | vs. Collins | 37 | | ⇄ |
| Taylor County | 45 | vs. Green County | 42 | | ⇄ |
| Todd County Central | 38 | at Hopkins County Central | 35 | | ⇄ |
| Trigg County | 49 | vs. Fort Campbell | 6 | | ⇄ |
| Trinity (Louisville) | 31 | at La Salle (Cincinnati), OH | 10 | | |
| Union County | 54 | at Murray | 30 | | ⇄ |
| West Jessamine | 49 | vs. Harrison County | 41 | | ⇄ |
| Western Hills | 20 | vs. Garrard County | 14 | | ⇄ |
| Wheelersburg, OH | 49 | at Ashland Blazer | 7 | | |
| Woodford County | 54 | vs. Tates Creek | 0 | | ⇄ |
| Saturday, September 10, 2022 |
| Caverna | – | at Berea | – | 4:00 PM | ⇄ |
| Johnson Central | – | at Ironton, OH | – | 7:30 PM | |
| Moore | – | at Webster County | – | 1:00 PM | ⇄ |