Royce O'Neale added 11 points for the Pioneers (17-8, 13-2 Western Athletic), who have won six straight games and 13 of 14.
Denver used a 13-1 run to take control of the game with a 28-12 advantage with 2:20 remaining before halftime.
San Jose State, which trailed 28-14 at intermission, got no closer than 12 points in the second half.
The Pioneers shot 53.3 percent (24 of 45) from the floor.
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.
The Central Intercollegiate Athletic Association says it won't move its headquarters, its basketball tournament or other conference championships from North Carolina, despite