North Carolina (21-7, 9-5 Atlantic Coast Conference) had a chance to send the game into overtime in the waining seconds, but Diamond DeShields' three pointer from the top of the arc rolled off the rim to cap a tough shooting night for the Tar Heels.
Carolina shot just 26.8 percent for the game, a season low, and was held under 65 points for the first time all year.
Tied at 36-36 midway into the second half, DeShields finished off a mini 7-1 run to give UNC its largest lead of the game, 43-37, with 6:55 to play.
Momentum swung back into Tech's favor by scoring nine-straight points to regain a 46-43 with less than two minutes left.
DeShields, fouled on a three-point attempt, made the first two free throws, but missed the last one to get within 46-45, however, Panousis basically sealed the win with four shots from the charity stripe in the final 19 seconds.
Xylina McDaniel had 13 points and eight rebounds, while Stephanie Mavunga had 10 points and seven rebounds to lead the Tar Heels.
DeShields and Allisha Gray combined to shoot 4-for-26.
Virginia Tech (13-14, 3-11) ran out to a 19-7 lead as Panousis drained three shots from distance in the opening eight minutes of play. She would score a game-high 24 points for the Hokies.
The UNC defense clamped down to hold Tech scoreless for the next nine minutes, allowing the Tar Heels back into the game.
Carolina took its first lead at 20-19 on the second of two free throws from Gray at the 3:50 mark of the first half, capping a 13-0 run for the Tar Heels.
Panousis snapped the long scoreless stretch for Tech with a runner, but Mavunga converted a three-point play to give Carolina a 23-21 lead.
Uju Ogoka's late bucket put Tech in the lead at intermission, 25-24.
Carolina plays at No. 2 Notre Dame on Thursday at 7 p.m., on ESPN3.