John Santiago rushed for 117 yards and three touchdowns in the team's first game as the Fighting Hawks (7-4, 4-3 Big Sky).
Santiago scored on runs of 14, 15 and 5 yards in support of Keaton Studsrud, who completed 17 of 20 passes for 255 yards and two scores.
The Hawks rolled up 474 yards of total offense. They took charge in a 21-point second quarter and went into halftime leading 28-0. North Dakota has won three straight games to give itself and outside shot at a playoff berth.
The FCS playoff field will be announced on Sunday.
Chris Brown had 211 yards passing for Cal Poly (4-7, 3-5), which entered the game averaging 410.7 yards rushing, but managed just 153 against the Fighting Hawks.