Freshman Jewell Loyd added 19 points on 8-of-10 shooting for the Fighting Irish (3-0), who jumped out to a 12-0 lead and never looked back, pushing it to 26-7 midway through the first half before taking a 48-12 lead at the break.
"I thought we played really well at both ends of the floor," Notre Dame coach Muffet McGraw said. "Natalie Achonwa, that's a remarkable line. That's amazing. Twenty-two points, 10 rebounds, no turnovers in just 18 minutes."
The Bears resorted to fouling Achonwa and Ariel Braker in the post to try and stop the easy baskets, but the pair combined to hit 10 of 13 at the free throw line. Notre Dame outrebounded Mercer 52-27 and outscored the Bears 60-12 in the paint. Braker had 12 points and five rebounds.
Achonwa, who posted her third career double-double, was quick to credit her teammates.
"I think our guys did a great job of finding us," Achonwa said. "We were trying to take advantage of the height differences and I think I just tried to hustle and get up the court, and the guards did a great job of seeing the floor and tossing it up in the air."
Notre Dame's aggressive defense forced 20 turnovers and the Irish shot nearly 54 percent (37 for 69).
Tabitha Bradshaw scored 10 points to lead Mercer (3-1), which was limited to perimeter shot attempts and hit only 26
Mercer coach Susie Gardner said she accepted Notre Dame's offer to start a home-and-home series last season for the benefit of former Irish player and Atlanta native Fraderica Miller, who could call the game somewhat of a homecoming with Mercer located in Macon, Ga. The Irish won that game 128-42, setting or tying eight school scoring records.
"I've learned my lesson," Gardner said. "Our program is just not ready for this, at this level."
She said she doesn't think such lopsided affairs benefit either team or help them prepare for their conference schedules.
"We're not like anyone in their league and they're not like anyone in our league," Gardner said. "It's just a game on the schedule."