Lincoln, Neb. Ade Dagunduro scored 15 points to lead Nebraska, and the Cornhuskers used tough defense to pull away from Charlotte, 67-48.
The Huskers (20-12) advance to a second-round game Monday at Mississippi, which defeated UC Santa Barbara, 83-68.
Charlotte's postseason ride ran into a Big Red roadblock on Wednesday night.
The 49ers' usually reliable defense was lacking, and Nebraska rolled to an easy victory at the Bob Devaney Sports Center in the first round of the National Invitation Tournament.
Charlotte finished 20-14 - the fifth 20-win season in Bobby Lutz's 10 years as head coach, and eighth with a postseason bid (five NCAA, three NIT).
While the 49ers exceeded expectations this season - they were a preseason pick to finish 10th in the Atlantic 10 Conference - and utilized eight new players, the ending was still a sour note.
The loss was Charlotte's worst of the season.
Prior to Wednesday, the 49ers had lost by double digits just three times, twice against league rival and eventual tournament champion Temple.
Charlotte struggled to muster consistent offense in the first half. The 49ers kept it close and led 16-15 with 8:05 left in the half when Nebraska went on a 12-4 run to take a 29-19 lead on Paul Velander's three-pointer.
Cookie Miller's three-pointer with 28 seconds left gave the Cornhuskers a 33-21 lead at halftime.
The 49ers cut the deficit to 10 on their first possession of the second half on a jumper from Charlie Coley, but never got any closer.
The victory improved Nebraska to 20-12 on the season.
After an up-and-down regular season that saw highs in the form of victories of NCAA Tournament teams Kansas State, Texas A&M and Oklahoma, the Cornhuskers turned things in the right direction and proved to be a tough out in the first round of the Big 12 tournament, losing to No. 4 Kansas by just 10 points.