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.
Former Kentucky guard Ed Davender, the only Wildcat with at least 1,500 points and 400 assists, has died. He was 49.
Guard Naz Mitrou-Long, whose 2015-16 season ended in December due to hip problems, has been granted a hardship waiver for the coming season, Iowa State said.
As the Sooners look to life without superstar Buddy Hield and his sidekicks, it's clear their unseasoned players will need to grow up fast.