It was a third straight loss for the Tigers, who fell to 14-9 overall and 2-3 in the SEC. Mississippi State improved to 17-6 overall and 3-2 in the conference.
The Tigers will send their ace to the mound on Sunday to try to salvage the third game of the series as Derek Varnadore, who is 3-0, goes against MSU lefty Nick Routt, who does not have a decision this year.
Auburn gave the Bulldogs eight first inning runs as Will Irvin was charged with seven of them. He gave up six hits and walked a batter before being pulled after 2/3 of an inning. Reliever Slade Smith also struggled, giving up a dozen hits in 4 1/3 innings.
The Bulldogs pounded out 21 hits to thwart any hopes of a comeback for the 20th-ranked Tigers.
"We will regroup, flush this one out of our system and try and win one here, which is obviously a very important game tomorrow," Auburn coach John Pawlowski said.
The bright spots for the Tigers included Casey McElroy extending his hitting streak to 18 games plus Cullen Wacker and Bobby Andrews having a pair of hits apiece while Dillon Ortman pitched three scoreless innings of relief for the Tigers.
Ryan Collins led the Bulldogs going 4-4 with two runs and two runs batted in. MSU pitcher allowed just five Auburn hits in 7 1/3 innings to improve his record to 4-1.