Peter Beale-Wirsing's three-point play with 13:43 remaining pulled San Diego Christian within three, 42-39, but Santa Clara (2-0) used a 15-4 run to pull away for good.
San Diego Christian shot just 38.3 percent from the field, but used an 18-10 advantage on the offensive glass - and 18 second-chance points - to keep the game, which was tied at 29 going into halftime, competitive.
Beale-Wirsing scored 20 points and pulled down 14 rebounds. Derrick Thompson added 12 points and Daniel Nielsen scored 11.
The game served as an exhibition for NAIA San Diego Christian.