Santa Clara (5-0) remained unbeaten by hitting 51 percent of its shots and converting 17 of 21 free-throw attempts.
Raymond Cowels III scored 12 points for Santa Clara, hitting four 3-point shots.
Eastern Washington (1-5) had a 27-19 scoring advantage off the bench, but could not remain in contention.
Collin Chiverton scored 19 points, including 4-of-8 shooting from 3-point range.
Eastern Washington had a 39-29 rebounding advantage, getting a game-high eight from Justin Crogsile.
Indiana guard James Blackmon Jr., who averaged 15.8 points in 13 games before being injured last season, has withdrawn from the NBA draft.
Isaiah Briscoe has decided to withdraw from the NBA draft and will return to Kentucky for his sophomore season. Marcus Lee intends to transfer.
The Big 12/SEC Challenge will again feature Kansas and Kentucky, this time at Rupp Arena. That's not the only exciting matchup in next season's midseason conference showdown.