Mariota led the Ducks to a 36-5 record and set an NCAA record by throwing a touchdown in all 41 of his career starts.
The 21-year-old’s decision to enter the draft comes just two days after the Oregon lost 42-20 to Ohio State in the National College Championship game.
The versatile quarterback, who set a Pac-12 Conference record with 58 total touchdowns this season, is widely regarded as one of the top overall prospects in this year’s draft class.
Mariota is expected to vie with Florida State signal caller Jameis Winston to be picked first overall by the quarterback-needy Tampa Bay Buccaneers.
“After meeting with my family I have decided to forego my final year of eligibility and apply for the 2015 NFL Draft,” Mariota announced on Wednesday.
“My four years at the University of Oregon have been an awesome experience. I will miss being with my team-mates.
???Being a part of this team was something special that I will always treasure.”
The draft takes place April 30-May 2 in Chicago.