Jordan Crawford posted 19 points for the Musketeers (21-7, 12-2 A-10), who are tied with Temple atop the conference after Temple's win over LaSalle later Sunday. Jason Love added 16 and Mark Lyons scored 10 in the winning effort.
David Gonzalvez hit four threes en route to 18 points and nine rebounds for the Spiders (22-7, 11-3), whose eight-game win streak came to an end. Kevin Anderson scored 17 and Justin Harper added 15 in defeat.
Two from the line by Holloway gave Xavier a 77-72 edge, but a three-point play by Ryan Butler made it a two-point contest with 1:40 left in the second OT.
Love made 1-of-2 at the line with 13 ticks to make it 78-76 for the home team, then Harper missed a contested layup in the final second.