Walsh finished 18 of 27 after relieving starter Clint Chelf on the Cowboys' third series. Jeremy Smith rushed for 102 yards and two touchdowns on 15 carries for Oklahoma State (1-0), which piled up 432 yards on offense after struggling for most of the first half.
Tyler Russell 10 of 16 for 133 yards before being helped off the field and taken to the locker room in the third quarter after being brought down on a scramble. Dak Prescott replaced Russell, throwing for 89 yards on seven of 17 passing.
LaDarius Perkins rushed for 50 yards on 16 carries and caught three passes for 52 yards for the Bulldogs (0-1), which had only 333 yards of offense and had trouble keeping drives going, finishing two of 16 on third down conversions.
Oklahoma State's defense also had three sacks and intercepted two Mississippi State passes. Oklahoma State's offense gained only 67 yards with less than four minutes remaining in the first half before Walsh got going.
Walsh worked the quarterback keeper three times for gains of 46 yards down the left sideline, 12 yards down the left sideline to the MSU 3 and capping it off with a 3-yard touchdown run to give the Cowboys a 7-3 lead with 2:16 left in the half.
OSU continued the offensive momentum in the second half, driving 75 yards in 11 plays to take a 14-3 lead on a Smith 1-yard run with 10:41 left in the third.
Smith tacked on a 20-yard touchdown run to begin the fourth quarter to up the lead to 21-3.
The Bulldogs looked to respond before the half as Jameon Lewis weaved the kickoff return 66 yards to the OSU 34, but a holding penalty and a sack by Tyler Johnson stopped the drive.
Mississippi State marched down the field in 57 yards on 13 plays taking over six minutes off the clock, but the Bulldogs were only able to get Devon Bell's 40-yard field goal to take a 3-0 lead. Russell was 5 of 7 on the drive for 58 yards.