Iowa State (2-1) shot 65 percent from the field.
Harouna Mutombo led Western Carolina (2-2) with 19 points.
The Cyclones led just 38-34 at halftime, but broke it open after the break, hitting on 77 percent of its shots (20 of 26) from the floor in the second half.
Royce White scored 14 of his 17 points in the second half. Chris Allen had 13 points and reserve Tyrus McGee added 12 on four 3-pointers for the Cyclones.
The game was played as part of the South Padre Island Invitational. Iowa State continues tournament play Tuesday at home against Northern Colorado before heading to South Padre Island for games Friday and Saturday.