Guice was expected to forgo his season season and he announced his decision via Twitter.
"Nothing will ever replace LSU in my heart because you had a big part in raising me from a young boy to becoming a man. To my family, thank you for everything. I promise not to let you down. I promise I'm going to come back and get my degree one day," Guice said in a video message he posted.
Guice will follow in the footsteps of former Tigers running back Leonard Fournette, who exited the program a year ago and wound up the No. 4 overall pick of the Jacksonville Jaguars.
The 5-foot-11, 220-pound Guice rushed for 1,251 yards and 11 touchdowns this past season. He was even better as a sophomore, piling up 1,387 rushing yards and 15 touchdowns.
Guice, projected as a first-round pick, set school records for the longest run (96 yards) and rushing yards in one game (285).
A native of Baton Rouge, La., Guice leaves with a career average of 6.527 yards per carry, also an LSU record.
Rob Rang, a senior analyst for NFLDraftScout.com, rated Guice as a top-10 pick before his injury-plagued junior season and still has him ranked in the top 25.