Sams, who completed 11 of 16 passes, also rushed for 78 yards on 10 carries through three quarters. Ryan Ross rushed for 73 yards and one touchdown. Tavarious Battiste caught five passes for 67 yards for McNeese State (3-0).
Grant Ashcraft, who replaced Sams, threw for 67 yards on 6-of-7 passing.
The Cowboys racked up 506 total yards - 265 rushing and 241 passing - while limiting Mississippi College to 99 yards rushing and just 15 yards passing.
This was the first shutout for the McNeese State defense since the 2012 season when the Cowboys beat Lamar 35-0.
The Choctaws picked up their initial first down midway in the second quarter, trailing 20-0.