The fourth-seeded Explorers fell behind by as many as 12 points. Tyrone Garland led La Salle with 17 points. Tyreek Duren added 16 points and Jerrell Wright scored 13 points.
Explorers senior Ramon Galloway, the conference's No. 2 scorer during the regular season with a 17.4-point average, made just one of 10 attempts from the field - missing all seven of his three-point tries - and finished with four points.
La Salle was hurt by the absence of 6-foot-11 center Steve Zack, who sat out with a sprained left foot. The Explorers played the 6-8 Wright with four guards for most of the game and the Bulldogs held a big 41-23 advantage on the boards.
Trailing 64-52, the Explorers scored six straight points, including Sam Mills' three-point basket, to cut the deficit in half with five minutes to play. But that would be La Salle's final points of the game.
After a turnover, La Salle had a chance to trim the gap to four, but Galloway missed the front end of a 1-and-1. Clarke answered with a three-point basket for Butler and the Explorers had no answer the rest of the game.
Clarke, who missed the Jan. 23 game between the two teams, won 54-53 by La Salle, with an injury, led Butler with 14 points.
La Salle shot 50 percent from the field in the first half and trailed by only 37-35 after falling behind by nine in the period. Duren and Garland led the Explorers with 11 points.
But the Explorers went cold in the opening stages of the second half, scoring just five points in the first seven-and-a-half minutes. The Bulldogs eventually built their lead to 10, 50-40, on a three-point play by Kameron Woods with 12 minutes, 47 seconds to play.
After La Salle reduced the deficit to six on a three-point basket by Duren, Butler steadied itself and extended it margin to 12 when a driving layup by Roosevelt Jones made it 64-52.
The Bulldogs got off to a hot start, making six of their first seven shots from the field, and took a 22-13 lead on a three-point play by Khyle Marshall with 7:22 to play in the first half. Trailing 24-16, La Salle uncorked an 8-0 run, ending on two free throws by Galloway following a technical foul called against Butler coach Brad Stevens with 5:16 remaining.
The Explorers later went into the lead thanks to six straight points by Garland, whose three-point basket put his team ahead 32-31 with 3:13 left. But La Salle managed just one bucket - another trey by Garland - the rest of the way and Butler led 37-35 at the break.
Contact Joe Juliano at jjuliano@phillynews.com. Follow on Twitter @joejulesinq