Pennington took an early 7-0 lead on a 10-yard touchdown run from quarterback Noah Allison, who added the extra point himself.
Locust Fork came back with a touchdown in the second quarter and the game was tied 7-7 at the half.
The third quarter proved to be the difference as the visiting Tigers outscored the Hornets 13-0 in the period.
Pennington got a 1-yard touchdown run by Sheldon Blythe and a 12-yard run from Travis Haynes to extend the lead to 20-7 after three quarters.
Locust Fork appeared to be in good shape after cutting the Tiger lead to 20- 13 five minutes into the final quarter.
However, Pennington put together a numbing drive to end the game, pounding out several first downs in a possession that ate up more than seven minutes, and the Hornets never touched the ball again.
Locust Fork pounded out 300 rushing yards but failed to complete either pass attempt on the night.
Jarrett Peeples led the Hornets with 108 yards and a touchdown on just 14 attempts. Hunter Neeley added 96 yards and a score on 10 rushes and Drew Rogers chipped in 80 yards on 15 carries.
The Tigers put up 303 yards of offense – 177 on the ground, 126 through the air.
Allison led the Tiger offense, rushing 17 times for 76 yards and a score and completing 8 of 11 passing for 126 yards.
All eight of Allison’s completions went to Cole Littleton.
Luke Cassity led the Tiger defense with 23 tackles, 13 unassisted, and a fumble recovery.
Locust Fork dropped to 1-3 on the year, 1-1 in the region, and will travel to Susan Moore (1-2, 0-1) this week.
Pennington improved to 3-1, 2-0, and will host Hanceville (1-3, 0-2) Friday night.