Derrius Guice broke loose for touchdowns of 61 and 20 yards early in the third quarter, and LSU used a slew of big plays in the second half to break open what had been an unexpectedly close game and defeat Southern Mississippi 45-10 on Saturday night.
LSU had two one-play touchdown drives - an 80 yard catch-and-run by D.J. Chark and a 63-yard reception by Malachi Dupre on Danny Etling's long heave.
LSU safety Jamal Adams helped the Tigers pull away when he forced Golden Eagles running back George Payne's fumble and then recovered it at the USM 26-yard line, setting up Guice's second score.
In the span of the third quarter, LSU (4-2) turned a 10-all tie into a 38-10 lead.
Guice finished with 162 yards on 16 carries in his third start this season in place of Leonard Fournette, who is recovering from a left ankle injury and has not played since LSU's loss at Auburn on Sept. 24.
The 5-foot-11, 212-pound Guice has rushed for at least 155 yards in each of his starts.
Dupre added another touchdown on a 23-yard reception in the fourth quarter. Chark also scored a 19-yard rushing touchdown on an end-around in the first half.
Etling finished with his best numbers since taking over as starter in the third game of the season, completing 11 of 18 passes for 276 yards and three TDs.
Guice gave LSU the lead for good when he sprinted through a gaping hole blown open by guard Maea Teuhema, center Andy Dodd and tackle K.J. on the left side of LSU's offensive line and then galloped into the open field for a career-long scoring run. While Guice's first touchdown demonstrated his break-away speed, his second showcased his elusiveness as he darted forward and then cut outside to elude would-be tacklers.
Ito Smith scored the lone TD for Southern Miss (4-3) on a 1-yard run that gave Southern Miss its only lead of the game at 7-0. Golden Eagles quarterback Nick Mullens completed 25 of 36 passes for 161 yards.
Southern Miss dominated time of possession, 37:59 to 22:01 and the Golden Eagles ran 73 total plays to LSU's 42, but that hardly mattered with LSU getting big plays on both sides of the ball in the second half.
LSU, which was among the leading vote getters among unranked teams in the AP Top 25 Poll this past week, could very well be ranked again in the next poll after a second resounding victory under interim coach Ed Orgeron, who took over after Les Miles was fired four games into the season.
Southern Mississippi: The Golden Eagles have play makers and the ability to be competitive in spurts with Power-5 conference teams, but need help for a beleaguered defense that has now allowed 100 points in its last two games.
LSU: The Tigers have the kind of elite talent to turn it on suddenly and crush a heavy underdog from a mid-major conference. And the Tigers just might be trending in the right direction to become a formidable foe for Southeastern Conference opponents as well, particularly at home.
Southern Mississippi: The Golden Eagles are off next week, then resume action at home against Marshall on Oct. 29.
LSU: The Tigers host No. 12 Mississippi in a pivotal mid-season clash in the SEC West race. It is also the first of five straight SEC games to close the season for LSU.
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