Wake Forest (6-5) built a 17-0 lead on the strength of a pair of touchdown passes from MacPherson, who found Ira Williams for a 12-yard score and Fabian Davis on a 47-yard pass play.
A two-yard run by Fres Staton gave the Demon Deacons a 24-7 halftime edge.
Northern Illinois (6-5) climbed within 24-21 on Thomas Hammock's one-yard touchdown run with just under seven minutes left in the third quarter. But Tarence Williams scored on a 12-yard run and John Stone added a 13-yard rushing touchdown for a 38-21 advantage.
The Huskies closed the deficit to 38-35 with 6:25 left on a 27-yard run by Michael Turner. They got back the ball with three minutes left on their own 34-yard line, but Chris Finlen threw an incompletion on fourth down and Wake Forest ran out the clock.
Nine of the Demon Deacons' 11 games this season were decided by seven points or less.
Tarence Williams broke the 1,000-yard rushing plateau and posted his seventh 100-yard rushing effort of the year.