Walsh was 24-for-27 passing for 326 yards before making way for senior Clint Chelf, who threw for 192 yards and two TDs in the fourth quarter.
Walsh, a sophomore, had been promoted to the starting job at Chelf's expense after last week's win over Mississippi State.
Josh Stewart caught five passes for 97 yards and a TD for the Cowboys (2-0). Six different Oklahoma State receivers caught TD passes.
Texas-San Antonio (1-1) staged a late rally, scoring four touchdowns in the fourth quarter. The Roadrunners had 308 passing yards from Eric Soza but managed only 87 rushing yards.