The sixth-seeded Tar Heels (23-8) trailed 39-27 at halftime and 62-61 before DeShields' 3. She hit two clinching free throws with 10.4 seconds left, sending UNC into Friday's quarterfinals against eighth-ranked and third-seeded Maryland.
Carolina overcame a 14-point deficit that Wake had built late in the first half, marking the most points the Tar Heels have overcome this season in a win.
Dearica Hamby scored 29 points and Chelsea Douglas added 20 for the 11th-seeded Demon Deacons (15-16) in a game delayed more than 20 minutes by a power outage early in the second half.
Wake Forest shot 59 percent before halftime, but went 6-for-23 (26 percent) afterward in its 12th straight loss to UNC dating back to 2004.
UNC played the second half without second-leading scorer Allisha Gray, who hit her head on the court while being fouled late in the first half.
Brittany Rountree filled in for the ailing Gray, starting the second half in her place. She scored seven points on 2-of-4 shooting before fouling out with two minutes left in the game.
Carolina held a 23-0 advantage in bench points over Wake Forest. While the Demon Deacons saw two players score 49 of their 65 points, the Tar Heels got a balanced effort in the victory.
All eight players that scored had at least six points with DeShields being the only one in double figures. Danielle Butts and Jessica Washington each had eight points off the bench. Gray and Xylina McDaniel had eight points each, while Stephanie Mavunga and Rountree tossed in seven apiece and Latifah Coleman had six points.