The Ramblers are in the field of 68 for the first time since their magical run to the Final Four in 2018 while the Bulldogs, with a 25-4 record, will wait to see if they receive an at-large bid on Sunday.
Cameron Krutwig led Loyola (24-4) with 20 points and eight rebounds while Braden Norris also tallied 20. D.J. Wilkins and Tremell Murphy paced Drake (23-4) with 20 points each.
The Ramblers shot 59.1 percent from the field and connected on 10 of 19 from three-point range.
Ramblers return to field of 68 with victory over Bulldogs
In a game of runs, Loyola went on a 10-0 run, capped by a three-point play from Jacob Hutson to give the Ramblers a 14-7 lead with 11:34 left in the first half.
A technical foul on Keith Clemons seemed to ignite the top seed and Loyola scored six unanswered points to take their first double-digit lead of the game at 24-14.
Drake responded with a 10-0 run to tie the game only to see Loyola go on a 10-2 spurt, with Norris and Tate Hall nailing triples to make it 34-26 Ramblers.
The Bulldogs responded again with five straight points, but a basket by Hutson sent Loyola into the locker room with a 36-31 advantage. The Ramblers shot 63 percent from the field in the opening 20 minutes.
A 17-6 run by Loyola to open the second half, keyed some more good long-range shooting, gave the Ramblers their largest lead of the game at 53-37, but an 11-3 run by Drake cut the lead to 56-48.
Norris' fifth three-pointer of the game stretched the lead back out to 65-52, but the Bulldogs mounted one final charge, closing the gap to 71-65 before Loyola iced the game with late free throws.