Nicholls shot 51.9 percent from the field and had only six players score.
Freshman Emani White scored 17 points off the bench, accounting for 13 in the first half as Nicholls (10-4 overall, 2-1 in conference) led 38-32 at the break.
KK Babin had 14 points and hit all six of her free throw attempts as Nicholls finished the day 15-of-16 at the line.
Rounding out the scoring was senior Alisha Allen with 13 and LiAnn McCarthy and Jenny Nash with 11 each.
Nicholls’ defense caused problems all night for McNeese, which made only 20-of-70 from the field (28.6 percent). The Cowgirls struggled from behind the arc as well, making just 5-of-27 attempts.
The win also snapped Nicholls’ 10-game losing streak against McNeese (6-8, 1-2).
The game was tied at 8 early on until White set the tone for the night as she banked home a desperation 3-pointer as the shot clock expired. McNeese tied it on a basket plus a free throw before Nicholls scored the game’s next seven points, including another 3-pointer from White.
Despite holding McNeese’s leading scorers, Ashley and Caitlyn Baggett, to a combined 10 points in the first 20 minutes, Nicholls never led by more than seven.
Leading 35-32 with a minute remaining, Nash sank a 3-pointer to give the Colonels a six-point advantage at the half.
In the second half, Babin came up with a big play early, saving the ball off a McNeese player on an offensive rebound to keep possession. On the inbounds, Babin hit a jumper to make the score 40-34.
The Cowgirls hung around, trailing 52-46 at the 13:15 mark before Nicholls shut down the McNeese offense during the next nine minutes.
During the stretch, the Colonels outscored McNeese 22-5 as McCarthy put a stamp on the run with a 3-pointer, making the score 74-51.
The Cowgirls cut it to 15 late before White made two free throws for the 78-61 final.
The Colonels out-rebounded McNeese 47-32, with Scott recording her second double-double with 11 rebounds. Babin chipped in with seven boards and had a game-high six assists. Nicholls connected on 7-of-21 from behind the arc, led by three 3-pointers each by White and Nash.
Ashlyn Baggett led McNeese with 17 points on 5-of-18 from the field.
The win was the Colonels’ first on the road at McNeese since the 2006-07 season and only its 13th victory overall in 53 meetings.
Nicholls returns to action Saturday at Southeastern Louisiana. Tipoff is scheduled for 2 p.m.