Manziel ran in two scores for the Aggies (7-2, 4-2 SEC), who churned out 693 yards of total offense and led 24-0 at halftime.
The Aggies won for the seventh time in eight games while Mississippi State (7-2, 3-2) lost its second in a row after going 7-0 to start the season.
Ryan Swope caught nine passes for 121 yards for Texas A&M. Ben Malena ran for 112 yards and a touchdown.
Manziel led the Aggies to scores on their first three possessions. The Aggies picked up 36 first downs in the game to 15 for the Bulldogs.