Mariota went 16-of-27 passing for 355 yards and carried the ball seven times for 43 yards as the Ducks (5-0, 2-0 Pac-12) extended their string of early-season routs, winning each of their first five contests by at least 39 points.
Bralon Addison (five catches, 158 yards) and Josh Huff (five grabs, 103 yards) each caught two scoring strikes, while Byron Marshall led Oregon's ground game with 122 yards on 23 carries.
The Buffaloes (2-2, 0-2) stumbled as Connor Wood was limited to 11-for-33 passing for 205 yards and two interceptions.
Paul Richardson made five catches for 134 yards and also threw a 75-yard TD pass for Colorado.
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