LSU's defense had all the answers for its ranked Tigers downed the 25th-ranked 6.
The hard-hitting conference clash was close through three quarters, but LSU opened up a 10-point lead when Jarrett Lee threw a touchdown to Rueben Randle early in the fourth.
Mississippi State's offense essentially went backwards the rest of the way, compiling 193 yards after totaling 1,176 yards in its first two games.
"I felt like the intensity of the defense was strong and that really ended up being the tale of the day," LSU head coach Les Miles said. "We're not playing perfect...but effort, intensity and style of play, we're getting there."
Lee was 21-of-27 for 213 yards and an interception, with Randle hauling in six passes for 98 yards for the Tigers (3-0, 1-0 SEC), who have won 12 straight and 19 of 20 against the Bulldogs.
Chris Relf was benched in the fourth quarter after throwing for just 96 yards with an interception on 11-of-17 efficiency for Mississippi State (1-2, 0-2), which was coming off a 41-34 setback at Auburn.
The Bulldogs had little chance against LSU's stout defense, which held quick- strike Oregon to 27 points in a huge season-opening win before keeping Northwestern State out of the end zone in a 49-3 romp on Saturday.
Even when faced with adversity in a hostile environment, the Tigers responded.
Trailing 16-6, the home crowd back in it when Johnthan Banks intercepted Lee five minutes into the final quarter.
The energy at a predominantly white-clad Davis Wade Stadium quickly dissipated, however, when an ineffective Vick Ballard was stopped for a five- yard loss and Tyler Russell threw incomplete on his first two passes in relief of Relf.
"We wanted to give him a chance and try and give our offense a spark," Bulldogs head coach Dan Mullen said.
Russell was picked off by Morris Claiborne deep in Bulldogs territory a little later, and Drew Alleman's fourth field goal -- a 29-yarder -- with under three minutes left sealed the outcome.
The Tigers chewed up nearly 7 1/2 minutes on a run-heavy opening possession, but they stalled after gaining 1st-and-goal from the seven, settling for a 21- yard Alleman field goal.
The Bulldogs shook off a three-and-out on their first touch and converted three third-down tries en route Derek DePasquale's 26-yard field goal in the closing seconds of the opening quarter.
The second stanza was a battle for field position, and Alleman booted a 42- yard field goal to cap a 10-play, 70-yard drive for a 6-3 lead at the break.
Relf had his first pass of the second half intercepted by Claiborne, but the hosts forced a punt and drove into field goal range, tying the game again on DePasquale's 42-yarder with 5:26 showing in the third.
Alleman countered with a 41-yard make, and Lee went 5-for-5 for 67 yards on what proved to be the game-sealing march, finishing it was a 19-yard toss to Randle in the right corner of the end zone with 11:56 remaining.
It was the first time in 105 meetings the two programs both came into the game ranked in the top-25...Lee fell six passes shy of tying the school record for most consecutive passes without an interception. Alan Risher holds the mark at 137...LSU has a 20-game winning streak in September...Claiborne has seven career interceptions...Spencer Ware led LSU with 107 rushing yards...The Bulldogs had scored at least 30 points in each of their previous five games dating back to last season...Ballard totaled 70 yards from scrimmage after rushing for 301 yards and four touchdowns over the first two games.