Marcus Paige had 11 points off three 3-pointers and Brice Johnson was the fourth North Carolina player in double figures with 10 points. Johnson also had eight rebounds.
Meeks, the 6-foot-9 sophomore, fought a stomach bug this week that had North Carolina coach Roy Williams wondering if he could go a few days earlier. Still, Meeks finished with his sixth double-double of the season.
Jaron Blossomgame had 13 points to lead Clemson (8-5), all in the second half.
The Tar Heels used a 20-5 run midway through the opening period to take control. Jackson scored nine consecutive points in the run that saw North Carolina's lead go from 2 points to 17. Moments later when Paige hit the second of his long-range baskets, the Tar Heels were up 32-12 and cruising with 3:27 left in the period.
The Tar Heels eventually grew the margin to 30 points.
North Carolina came in with a surging offense and defense - and showed that early on against the Tigers.
Clemson couldn't penetrate the Tar Heels' defense, settling for long jumpers that were off the mark or missing attempts inside with Johnson, Jackson and Kennedy Meeks pressuring every shot down low.
The Tigers ended with just five field goals to trail 39-17 at the half. It was Clemson's third half this season with five baskets, tying marks of futility in a win over Nevada and a loss to South Carolina this season.
The Tigers were 5 of 28 shooting (17.9 percent) in the first 20 minutes. Clemson doubled its field goal outpoint in the second half with 10 baskets, yet still finished shooting a season low 28.3 percent (15-of-53) for the game.
North Carolina: The Tar Heels have held all but one opponent this season to under 40 percent shooting. The eight straight to start the year was the longest such stretch in coach Roy Williams' 12 seasons at North Carolina. No. 1 Kentucky was the only opponent to shoot better than 40 percent (56.3 percent) in an 84-70 loss last month.
Clemson: Despite the loss, Tigers coach Brad Brownell is the program's only coach with a winning record in January (18-14) since the school joined the ACC in 1953.
North Carolina faces No. 14 Notre Dame at home Monday night.