Jerran Young came off the bench to score 18 points for Wright State (14-6, 5-2), which had won six of its past seven games coming in. The Raiders had won nine of the past 10 games in the series.
The Penguins' previous victory over the Raiders came on Feb. 23, 2007.
Youngstown State shot 24 of 48 from the field to Wright State's 25 of 63 and made 15 of 19 from the line to the Raiders' 5 of 10.
The Penguins led 28-25 at the half and 43-33 with 13:07 to go. Wright State closed to 46-42 at 6:51, but that was as close as they got.
DeSean Murray, who averaged 20.2 points as a sophomore at Presbyterian, will transfer to Auburn to play for coach Bruce Pearl.
Former Kentucky guard Ed Davender, the only Wildcat with at least 1,500 points and 400 assists, has died. He was 49.
Guard Naz Mitrou-Long, whose 2015-16 season ended in December due to hip problems, has been granted a hardship waiver for the coming season, Iowa State said.