Uiagalelei, a junior, finished his final season with 2,521 passing yards and 22 touchdowns to go with seven interceptions, as the Tigers went 11-2.
"God has brought me to this special place for a reason and I woudn't trade my time here for anything," Uiagalelei posted to Twitter on Monday. "I am very thankful and appreciative of the staff, trainers and my coaches for believing in me and pushing me every day to be the best I can both on and off the field.
"After careful consideration I would like to say that I have decided to enter the transfer portal."
From the opening week of the season, when Clemson struggled offensively before ultimately running away from Georgia Tech, there was buzz about backup Cade Klubnik -- a highly touted recruit -- replacing Uiagalelei.
Klubnik did play in that win over the Yellow Jackets, but after the outcome was long decided.
The future of the quarterback position became a weekly question in Swinney's news conferences thereafter. And as the season wore on, the coach continued to back Uiagalelei.
Even last week, as the Tigers prepared to meet North Carolina in the ACC championship game, Swinney said that Uiagalelei would start against the Tar Heels despite struggling in a 31-30 loss to South Carolina to close the regular season.
Swinney deflected blame for that loss from Uiagalelei, pointing to turnovers and drops from receivers as contributing factors.
However, during the win over the Tar Heels, things changed and Klubnik came off the bench to lift the Tigers to a 39-10 win. It was their seventh conference title in eight years.
Uiagalelei started the first two drives and struggled, going 2-of-5 for 10 yards. Both of his drives ended in three-and-outs. Klubnik then came in, led a scoring drive and played the rest of the game, going 20-of-24 for 309 total yards and two total touchdowns.
Afterward, Swinney said the plan heading into the game was for Klubnik to come in on the third series no matter what. Once Klubnik started moving the ball down the field, there was no turning back.
Swinney said Klubnik will start the Capital One Orange Bowl against Tennessee on Dec. 30.
"Things have to happen the way they're supposed to happen, and tonight, that's the way it went, and Cade was ready," Swinney said after the win. "You got a chance to see what he can do. He played in rhythm, guys made plays for him. He's really, really fast. He can really make plays with his legs. It was a great night and a glimpse of our future and what it looks like at Clemson."
The 6-foot-4, 235-pound Uiagalelei was one of the top recruits in the country out of St. John Bosco High in Bellflower, California. Over 35 games in three seasons for Clemson, he threw for 5,681 yards and 36 touchdowns with a 59.8% completion rate and 17 interceptions.
The Associated Press contributed to this report.