Arianna Roberson had 10 points and 10 rebounds off the bench and Ashlon Jackson added 12 points for Duke (26-8), which never trailed.
The Blue Devils advanced to the Sweet 16 for the third straight season and 20th time overall. They will play No. 2 LSU, a 101-47 winner over No. 7 Texas Tech, in the Sacramento 2 Regional.
Baylor (25-9) was held to its worst offensive output of the season. The Bears managed just eight points in each of the first two quarters and finished 0-of-14 from beyond the arc, failing to make a 3-pointer for the first time this year. They shot 30.2% overall.
Taliah Scott, who scored 24 points in a season-opening 58-52 win over Duke in Paris, led Baylor with 13 points on 3-of-17 shooting.
Duke jumped ahead 9-0 as Baylor missed its first six shots and didn't score for 5:56. Nine of the Bears' 23 turnovers came in the first quarter,
The Blue Devils widened their lead to 38-16 at halftime before increasing it to 29 points in the second half.