Dee Hart rushed for 139 yards and two touchdowns, while Treyous Jarrells added 121 yards and a score of his own for Colorado State (1-0). Garrett Grayson threw for 134 yards and a touchdown on 13-of-23 passing.
Sefo Liufau completed 24-of-39 pass attempts for 241 yards and a pair of touchdowns in the losing effort for Colorado (0-1). Nelson Spruce had 104 yards and two touchdowns on seven catches.
After stumbling on their first drive, the Buffaloes showed a spark on their second, as Liufau connected with Spruce for a 54-yard touchdown pass.
A 23-yard field goal from Will Oliver pushed the Buffaloes to a 10-0 lead early in the second quarter.
Despite struggling on offense for most of the first half, the Rams managed to enter intermission trailing just 10-7 thanks to an eight-yard touchdown run from Hart just before the break.
The Rams and Buffaloes traded touchdowns in the third quarter, with Liufau connecting with Spruce for a 12-yard score and Jarrells scoring on a three- yard touchdown run.
Colorado State took its first lead of the game early in the fourth quarter when Grayson tossed a 16-yard touchdown pass to Rashard Higgins.
A three-yard rushing touchdown from Hart later in the period extended Colorado's advantage to 28-17.
The Rams really put the game out of reach on a 52-yard field goal from Jared Roberts with under three minutes to play.
Despite the win Colorado still leads the all-time series, 62-22-2.