Lenoir had 124 yards receiving on nine receptions and Javon Williams Jr. had 113 yards rushing on 10 carries.
The Salukis (6-4, 4-2 Missouri Valley) scored on five of six possessions in the first half - four produced touchdowns - and they built a 30-0 lead by intermission. Southern Illinois piled up 555 yards of offense and 26 first downs, which helped offset three turnovers.
Southern Illinois now has won four straight following a three-game losing streak.
Peyton Huslig threw for 193 yards and two touchdowns for Missouri State (1-8, 1-5).
Following 4-2 start last year, the Bears now have lost 13 of their last 14 games.
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