Max Kenyi led Seton Hill (9-7, 6-6) with 20 points, five rebounds and three steals.
The game didn't start poorly for UC when Quincy Washington took the opening tip and dunked it, and Humphrey hit a 3-pointer to get it to 5-0 just 39 seconds into the game.
There were three lead changes in the contest and one tie, but when Perry hit a 3-pointer with 14:16 left in the game, Seton Hill didn't trail again.
Downey searched helplessly for a combination that would work, and played seven players at least 12 minutes.
The University of Charleston was just 10-of-31 from the floor in the second half and 5-of-16 from 3-point range, three of which came in the final 6:31 to cut two nine-point leads to six and an eight-point lead to five.
"Tempo is big for us," said Seton Hill assistant coach Josh Turnpaugh, filling in for head Coach Tony Morocco, who stayed at home with the flu. "Those guys are so athletic, so well coached and so good in the open court and we wanted to do the best we could to negate that.
"Lipkins playing limited minutes definitely is a bonus. That hurts them because he's a phenomenal player, but our guys were able to persevere."
Downey wouldn't put the loss on his team's win over West Liberty, or that Lipkins was severely limited.
The Golden Eagles get right back at it on Thursday when they host Wheeling Jesuit University - the team that knocked them out of the NCAA Division II Atlantic Region Tournament last year.
"I wasn't nice to them, I told them the way it was (last week)," Downey said. "I have to find a way to get it through to them, maybe this was it. If it doesn't after you get your butts kicked like this, it's not going to I guess. I'd do anything to squeak that thing out tonight, but we couldn't get a stop when we needed to and they'd get a shot when they needed to. They did everything they needed to do to win."
Contact Assistant Sports Editor Rich Stevens at richstev...@dailymail.com or 304-348-4837.