The Blue Devils improved to 20-0 on the season to match the best start in school history and their ninth straight 20-win season.
Duke remained one of only two unbeaten teams in men's and women's college basketball.
Duke shot 60.6 percent from the field in the second half marking the second straight game the Blue Devils have shot over 60.0 percent in the second half.
With her 16 points, Monique Currie moved into 20th place on the ACC career scoring list passing Tammi Reiss of Virginia. Currie now owns 1,855 career points.
Duke improves to 79-5 out of the 84 ACC contests.
Sophomore Wanisha Smith scored a season-high 16 points, hitting 7-of-7 field goals. She also dished out three assists in 25 minutes.
The Blue Devils shot 53.0 percent from the field marking the 15th time out of 20 games Duke has shot 50.0 percent or better.
Duke scored 97 points marking the 10th time this season the Blue Devils have scored 90 or more points.
As a team, Duke forced 23 Clemson turnovers marking the 17th time out of 20 games the Blue Devil defense has forced 20 or more turnovers.
Junior Lindsey Harding registered her seventh straight ACC game with double-figure points as she finished with 17. She also added two assists, one steals and five rebounds.
Sophomore Chante Black started in place of Alison Bales on the night. Black picked up two fouls in the first three minutes of the game and finished with four points and two steals in 14 minutes.
Alison Bales broke a string of 14 straight starts as she came off the bench to score seven points, grab seven rebounds and block four shots in 20 minutes.
Duke held a 36-11 advantage in bench points.
Laura Kurz broke a string of four consecutive games without a three-pointer as she hit one in the second half. Kurz finished with five points for the game.
Duke will next host second-ranked North Carolina on Sunday at 7:00 p.m. The contest will be aired live on ESPN2. The game is sold out, which marks the second straight sellout in Cameron Indoor Stadium.