The Demons (9-7 overall, 2-0 in the Southland) shot 63 percent after halftime while holding the Colonels (4-11, 0-3) to 38 percent aim, and forced nine second-half turnovers after coming up with only four in the first 20 minutes.
A James Hulbin 3-pointer with 4:05 to go gave Northwestern its first lead since 6-5, and the visitors never trailed again. The Demons got a pair of free throws by Gary Stewart with 9.5 seconds left to go ahead 80-76, and the Colonels sank a 3-pointer at the final buzzer to shorten the winning margin.
Northwestern shot a season-best 78 percent on free throws, sinking 29 of 37, including 8 of 13 by Mosley, a 42 percent shooter from the line this season. He sank two with 35 seconds to go lifting the Demons up 77-72 as Northwestern made 7 of 8 in the final 1:52.
Mosley, one point shy of tying his career scoring high, added 10 rebounds and six blocked shots. The Demons picked up 14 points by Louis Ellis, 12 from Shamir Davis and 11 - all in the second half - by Hulbin in the remarkable rally.
"We got aggressive defensively and made much better decisions with the ball," said 13th-year NSU coach Mike McConathy, whose team trailed 52-33 with 17:38 to go. "We got some transition baskets from our defensive pressure, and we shot free throws extremely well.
"It was a battle, but conference games always are going to be that way. Nicholls is very, very tough down here (31-6 in the last three years in Stopher Gym) and they played with tremendous heart tonight, and they were razor sharp in the first half."
Mosley moved into 25th place in NCAA Division I history with his fourth blocked shot. Mosley led the NCAA in blocks last year (4.9 per game) and now has 394 blocks. If he maintains this year's 3.9 pace (5th nationally) he will finish fifth all-time, ahead of Alonzo Mourning and trailing fourth-place Tim Duncan.
"The thing about him that's special is Mosley plays all over the floor. He isn't just a shot blocker," said McConathy. "He works so hard and it pays off. I'm glad he's going into the NCAA record book and before he's done, Lord willing, he's going to be near the top of that list, and deservedly so."
The Demons fought back into the game with a 16-2 run over six minutes, a stretch that expanded to a 22-5 advantage adding in the following two minutes. The Colonels repelled several bids by Northwestern to take the lead before a 10-0 burst started by a Mosley layup with 5:08 to go carried the Demons atop to stay.
"I don't care if it's by one or 21, we won," said McConathy. "We hadn't won here in our last four trips. Now we go into Saturday at home having shown some heart and resolve to get a tough win on the road."
NSU plays host to Central Arkansas Saturday at 1 in Prather Coliseum.