Nyla Brooks added 14 points, and Indya Nivar had 11 as the Tar Heels, hosting games on the opening weekend for the second year in a row, won a first-round game for the fifth straight season.
Fourth-seeded North Carolina (27-7) will meet fifth-seeded Maryland, a 99-67 winner over Murray State in the site's first game, on Sunday in the second round.
Mia Nicastro scored 21 points for No. 13 seed Western Illinois (26-6), which shot 30.4% from the field. The Leathernecks were 2 for 15 on 3-pointers. Nicastro shot 6 for 15 from the floor and 9 for 10 on free throws, coming up just short of her 24.2 points per game scoring average.
Grant made four of North Carolina's 10 3-point baskets. Harris had 12 rebounds as part of the Tar Heels' 47-32 edge on the boards.
North Carolina built a 23-11 lead while the Leathernecks made only three of their first 17 shots. The Tar Heels had a 38-24 halftime lead, holding Western Illinois to 25% shooting without a 3-point basket.
Western Illinois concluded its second winning season in the last eight years with its first NCAA tournament appearance since 2017.
In a matchup of former Atlantic Coast Conference rivals, North Carolina will next play Maryland with the right to advance to the Sweet 16.
- The Associated Press contributed