Winston, the reigning Heisman Trophy winner for the top-ranked Seminoles, originally had been suspended for just the first half against the visiting Tigers after a profane and sexually explicit outburst in the student union on campus earlier this week.
But Florida State decided to extend his suspension to the entire game because Winston was not entirely truthful or forthcoming regarding Tuesday's incident, a source told ESPN.
"Based upon the results of our continuing investigation of Tuesday's incident involving Jameis Winston, we have decided to not play him for the entire game against Clemson on Saturday night," interim Florida State president Garnett S. Stokes and athletic director Stan Wilcox said in a joint statement Friday night.
Winston joined his team on the field for warm-ups dressed in full uniform, including a helmet. After a discussion with coach Jimbo Fisher, Winston returned to the locker room. He then came back out wearing sweatpants, his game jersey (no pads) and a baseball cap. He and Fisher chatted again upon his return to the field.
Winston was seen shouting an obscene sexual phrase on campus Tuesday, the latest incident in which his off-field behavior has caused headaches for the team and university.
Florida State students began flooding Twitter as several witnessed the star quarterback allegedly stand on a table in or in the immediate vicinity of the student union and yell obscenities, mimicking a popular Internet video.
When announcing the original ban Wednesday, Stokes and Wilcox denounced Winston's behavior, calling it "offensive and vulgar" in a joint statement.
In a Wednesday news conference, Winston apologized for his "selfish" act.
"First of all, I want to apologize to the university, my coaches and to my teammates," he said. "I'm not a 'me' person, but in that situation, it was a selfish act, and that's not how you do things around here.
"I want to apologize to my teammates because I have now made a selfish act for them. That's all."
On Thursday, Fisher dismissed any criticism that Winston's original half-game suspension was too light.
"We're in charge. It's our team. That's our thought," he said. "We went with the consequences and we're ready to move on."
Tuesday's incident was just the latest involving Winston.
He was investigated in 2013 for sexual assault, but Willie Meggs, the state attorney for the Second Judicial Circuit, chose not to charge Winston in December. Florida State is still following through with its Title IX investigation into the matter.
Winston also was suspended from the baseball team for three games and ordered to perform 20 hours of community service after being cited for stealing $32 worth of crab legs from a local grocery store in April. There have been other minor run-ins with authorities, but no arrests.
Backup quarterback Sean Maguire, a sophomore who has completed 16 of his 26 attempts in mop-up duty during his FSU career, started in Winston's place against the Tigers.
"[Fisher] told me to be ready and said the game plan is not changing, this team is not changing, we're going to go out in the first half and do everything we usually would," Maguire said Thursday. "He had all the confidence in the world in me. He expects nothing to change just as so do I. ... It's a cliché answer but it's true: Nothing really has changed this week."
The winner of the Clemson-Florida State matchup has played in the ACC title game the past five years. Saturday will be the first game the Seminoles have played without Winston since the start of 2013, and they are 16-0 during that stretch.
ESPN's Tom Rinaldi and The Associated Press contributed to this report.