Ashley Wood scored a game-high five goals and Meghan Frederick tied her career-high with six assists for the Dukes who improved to 5-7 and 1-2 in the A-10.
Sarah Beckstead had a game-best 11 saves while recording her fifth win of the season.
Nora McGurkin led the Explorers (4-6, 1-2) with a pair of goals.
The Dukes exploded out of the gates scoring the first six goals of the match. Meghan Frederick set up Katie Rekart at the 24:11 mark to get DU on the board first. DU followed with three goals from Wood and a two from Sarah Cates before La Salle would get on the board. Back-to-back goals from McGurkin cut the Duquesne lead to 6-2 going into halftime.
Duquesne scored the first four goals of the second half - two from Wood and one from Alicia Krause and Frederick to take a 10-2 lead.
La Salle got a goal from Stefany McKee before Cailin Colegrove and Krause to give the Dukes their largest lead of the game at nine goals, 12-3 with 17:07 remaining.
The Explorers would score two more times before Janna Faulkner closed out the scoring with 2:35 left to give the Dukes a 13-5 win.
The Dukes outshot the Explorers 33-18. DU also picked up more ground balls (23 to 15) and had one more turnover (17-16). Next up for the Dukes is Saint Joseph's on Sunday. Match time is at noon.