SLU was outscored 41-26 in the first half and 44-32 in the second half.
SLU shot 30.9 percent from the field (17 of 55), 33.3 percent from beyond the 3-point arc (five of 15) and had 17 turnovers.
Kieron Achara led Duquesne (17-12, 7-9) with a game-high 24 points, and made all 12 of his free throw attempts. Gary Tucker added 14 points, while Reggie Jackson scored 12 and Kojo Mensah had 11 off the bench.
Duquesne shot 56 percent (28 of 50) for the game and made 24 of 29 free throw attempts.
The Billikens, who are 3-9 on the road this season, fell to 16-14 overall and 7-9 in Atlantic 10 games. SLU is now tied with Duquesne for 10th in the 14-team league, and only the top 12 teams make the conference tournament.
Saint Louis has now lost three of its last four games and was blown out in each of those losses. The Billikens lost by 17 points at Charlotte, by 20 against St. Bonaventure in the last game at Scottrade Center and then lost by 27 on Saturday at Duquesne.
The Atlantic 10 Tournament begins on Wednesday in Atlantic City, N.J.