Ja'Gared Davis returned a blocked field goal 77 yards for a score to help the Mustangs (3-2, 2-0 Conference USA) snap a 10-game losing streak to the Owls.
Sam McGuffie led Rice (1-4, 0-1) with 96 rushing yards and one touchdown. Nick Fanuzzi completed 27 of 43 passes for 276 yards but had two interceptions, one of which was returned for a score.
Padron was 24 of 32 with six of his passes going to Robinson. Cole Beasley added 158 yards on eight catches as SMU compiled 472 total yards.
The Mustangs' defense and special team were just as impressive. Sterling Moore scored the game's first points with 9 minutes left in the opening quarter when he intercepted a pass by Fanuzzi returned it 32 yards for a touchdown.
Youri Yenga blocked a field-goal attempt by Chris Boswell late in the third quarter, and Davis recovered it and rumbled 77 yards for a 28-10 lead.
Charles Ross scored on a 1-yard run to pull Rice to within 28-17 with 14:11 to play, but SMU scored on back-to-back drives to effectively put the game away.
The Owls cut their deficit to 14-10 early in the third when Phillip Gaines recovered a fumbled punt in the end zone, but they never got any closer.
SMU last beat Rice in 1986.