Mathews' night, which ended after three quarters, included a 59-yard touchdown that highlighted the Bulldogs' 24-point second quarter. It was the junior's sixth straight game with 100 or more yards.
Fresno State (3-3, 2-1 Western Athletic Conference) scored 34 unanswered points after San Jose State (1-5, 0-2) took an early 14-7 lead.
Lamon Muldrow had 73 rushing yards for the Spartans, and quarterback Jordan La Secla completed 17 of 27 passes for 143 yards and a touchdown.
Bolstered by a strong ground game, Colburn completed 7 of 12 passes for 117 yards before giving way to backups Ebahn Feathers and Derek Carr.