The Bulldogs closed the game with a 22-5 run, sparked by Timmy Bowers' clutch scoring and a trapping 1-3-1 zone defense.
Bowers converted a three-point play to tie the game with 5:06 left, then scored four straight points on a layup and two free throws to give Mississippi State a 55-50 lead with 2:12 remaining.
The senior point guard finished with 18 points.
"All our guys realize that this is pretty much my team," Bowers said. "I know we've got a lot of good players. I'm not a guy with a cocky attitude, going out there and telling everybody this is my team. But I'm the guy who is the leader out there. The guys trust me with the basketball."
Ole Miss (8-4) had its six-game winning streak snapped and lost to the Bulldogs for the fifth straight time.
Tommie Eddie had 13 points and a season-high 12 rebounds for the Rebels, while Justin Reed, their leading scorer, was held to 13 points on 5-for-16 shooting.
Reed's baseline jumper made it 49-39 with 8:06 left.
At that point, Mississippi State went to the zone and confounded the Rebels, who made only two field goals the rest of the way.
"We forced them to change to the zone. We knew it was coming," Ole Miss coach Rod Barnes said. "We just did not handle it well. We stopped attacking the basket."
The Bulldogs scored 12 straight points and took a 51-49 lead when Branden Vincent scored off a loose ball under the basket with 4:21 left.
Bowers took over from there.
"We wanted the ball in Timmy Bowers' hands every possession," Mississippi State coach Rick Stansbury said.
Bowers scored six points over the final 2:53.
"Timmy's our leader," Vincent said. "When it comes down to the clutch, it's going to be in Timmy Bowers' hands."
Lawrence Roberts had 11 points and eight rebounds for the defending SEC West champion Bulldogs.
Ole Miss built a 29-19 lead with its best half of the season.
The Rebels outrebounded the taller Bulldogs and held them to a season-low for first-half points, despite Reed playing only 9 minutes because of two early fouls.
Mississippi State scored nine straight points to open the second half, cutting a 10-point lead to 29-28 on Bowers' long 3-pointer.
The early spurt brought the large contingency of Bulldogs fans in Tad Smith Coliseum to life and had the place sounding a little like Mississippi State's Humphrey Coliseum.
From there it turned into a typical Ole Miss-State game, fiercely contested and competitive to the end.
"The difference tonight was they played hard for 40 minutes and we didn't," said Ole Miss' second-leading scorer Aaron Harper, who had only six points.
The last five games between the Rebels and Bulldogs have been decided by a total of 23 points.