Thomas had 594 rushing yards, 246 receiving yards and 10 total touchdowns this season despite being sidelined for nearly four games because of a right ankle injury.
He also excelled as a returner, running back four kickoffs and a punt for touchdowns in his three seasons in Oregon.
"I am officially withdrawing from the University of Oregon to pursue a professional career in the NFL," Thomas said in a statement. "I want to express my deepest appreciation and thanks to the University and all of my teammates, coaches and fans. I look forward to staying connected to the University and visiting the sidelines as often as possible."
Thomas' 5,345 total yards are third in school history after LaMichael James and Kenjon Barner. He holds Oregon records for kickoff return yards with 1,885 and his 17.1 punt return average.
The 5-foot-9, 170-pound Los Angeles native ran for two touchdowns in the Rose Bowl victory over Wisconsin after the 2011 season. The next season in the Tostitos Fiesta Bowl win over Kansas State, he ran the opening kickoff 94 yards for a touchdown.
"De'Anthony has been a spectacular talent in college football and has been a part of some of the most memorable plays in the history of the University of Oregon," Oregon coach Mark Helfrich said. "We wish him success going forward with his career."
Thomas also ran track for the Ducks, anchoring their 4x100-meter relay team.