Freshman Wade Korpi (3-1) took the mound for the Irish and pitched fairly well even though he suffered the loss. Korpi struggled early with his control, allowing two first-inning walks and a single, eventually surrendering a first-inning run.
The Irish fought back in the bottom of the second scoring their first run on a Greg Lopez RBI ground out to tie the game 1-1.
Central Michigan plated two more runs in the fourth fueled by back-to-back singles and an error to regain the lead 3-1.
Korpi eventually gave way to senior Scott Bickford. Bickford pitched an impressive fifth inning, but struggled in the sixth as Central Michigan plated another four runs in the top of the sixth on three singles.
Irish closer Ryan Doherty entered the game for Bickford and walked the first batter he faced, and then hit the next two Central Michigan hitters he faced before closing out the deciding sixth inning.
The Irish battled back in the bottom of the sixth scoring two runs, but they couldn't find their stroke at the plate.
Notre Dame scored just four runs on seven hits on the evening, and Irish coach Paul Mainieri said he was very dissatisfied in his team's focus on Wednesday.
"It was a disappointing night. I don't think we played a very good baseball game in most areas," Mainieri said. "Korpi did some really good things. He struck out eight batters and got some big outs, but he just walked too many batters.
"I don't think we played a very smart game in a number of ways. You credit Central Michigan. They played better than we did tonight."
The Irish (17-15) are now in a difficult situation. As the losses pile up for Notre Dame, Mainieri believes his team will likely have to play their way into post-season play.
"I'm resolved to the fact that we're going to have to win the conference tournament to get into the NCAA tournament," Mainieri said. "We've just had too many midweek losses that have hurt us if it comes down to a selection committee.
The Irish can take a step in the right direction this weekend and they face Connecticut this weekend in a three-game series at Frank Eck Stadium.
"We're going to go with (Dan) Kapala game one, (Tom) Thornton game two, and starting (Jeff) Manship game three," Mainieri said of his starters for the three-game series.