Jake Anderson added 10 points, 12 rebounds and five assists for the Cyclones, who built a 23-point lead in the first half and were never threatened after that.
Iowa State (2-0) trailed 9-7, then promptly erased any hopes the Hornets (0-2) had of staying close by scoring 29 of the next 33 points to take control.
The Cyclones had runs of 12-0 and 10-0 during that stretch and limited Alabama State to one field goal over a 10-minute span. Ahead 41-22 at halftime, Iowa State started the second half with an 11-2 burst and coasted from there.
Stephawn Brown led Alabama State with eight points.