LSU, which defeated the Rebels, 4-3 in 13 innings, on Thursday night, dropped to 29-10-1 overall and 9-7-1 in the SEC. Ole Miss improved to 30-10 overall and 10-7 in conference play.
Ole Miss centerfielder Auston Bousfield was 4-for-4 at the plate on Friday night, including a solo homer and three RBI, to lead the Rebels' 10-hit output.
Left-hander Christian Trent (5-0) earned the victory for the Rebels, working seven innings and limiting the Tigers to one unearned run on seven hits with two walks and five strikeouts.
Ole Miss reliever Scott Weathersby blanked the Tigers over the final two innings, recording four strikeouts.
LSU starter Jared Poche' (6-3) was charged with the loss as he allowed seven hits and four runs – two earned – in six innings with two walks and two strikeouts.
"I thought Jared Poche' gave us another courageous effort and really battled throughout the game," said LSU coach Paul Mainieri. "He wasn't quite as sharp as he usually is with his command, but he competed and kept us within striking distance. Unfortunately, we didn't play well enough to win and couldn't generate the offense we needed. To win in a place like this against a good team, you have to play very well and we didn't do that tonight.
"We'll look forward to tomorrow with a chance to win the series in a tough road environment."
Ole Miss took a 1-0 lead in the first inning on third baseman Austin Anderson's RBI single.
LSU tied the game in the third when Anderson misplayed a sharp grounder off the bat of first baseman Kade Scivicque, allowing rightfielder Mark Laird to score.
Ole Miss regained the lead in the bottom of the third on catcher Will Allen's RBI groundout, scoring leftfielder Braxton Lee, who had led off the inning with a single.
The Rebels, taking advantage of an LSU error in the inning, extended the lead to 4-1 in the fourth when Bousfield delivered a two-out, two-RBI single to plate two unearned runs.
Bousfield launched a solo homer against LSU reliever Cody Glenn in the seventh to increase the margin to 5-1.