Miller had an MRI on his throwing shoulder Tuesday morning, revealing the season-ending injury.
Widely tabbed as a Heisman Trophy contender this preseason, Miller suffered the injury during a noncontact portion of practice, just hours after the senior declared himself 100 percent healthy following offseason surgery to the shoulder. He was taken off the field under medical supervision, a source told ESPN on Monday.
Miller threw for 2,094 yards and 24 touchdowns and ran for 12 more scores in leading the Buckeyes to the Discover Orange Bowl last season.
Ranked fifth in the preseason Associated Press poll released Sunday, Ohio State is expected to be in the national title conversation.
The reigning two-time Big Ten Offensive Player of the Year, Miller first hurt the shoulder in the Orange Bowl. He had surgery that prevented him from contact in spring practice and was held out of several practices and scrimmages in August.
Redshirt freshman J.T. Barrett is expected to be the starter when the Buckeyes open the season Aug. 30 against Navy in Baltimore. Ohio State coach Urban Meyer said Saturday that redshirt sophomore Cardale Jones is the third-team quarterback.
Miller is one of the Big Ten's most decorated quarterbacks, and the falloff in experience to Barrett and Jones is huge.
Starting as a freshman, Miller has thrown 666 passes in his glittering three-year career. Barrett has never played in a game, and Jones has thrown only two passes.
Miller has run for 32 touchdowns and passed for 52, putting him in reach of many of Ohio State's career records for quarterbacks. Jones has run for one touchdown and has never thrown for one.
Barrett was an acclaimed recruit out of Wichita Falls, Texas, who watched with Jones last year as Miller took most of the snaps in the Buckeyes' 12-2 season. When Miller was hurt for most of the San Diego State, California and Florida A&M games with a sprained knee, senior Kenny Guiton had big games while leading Ohio State to victories.
But Guiton graduated, and the Buckeyes might have to adapt on the fly. Making that even more difficult is that Ohio State is without four of its five starting offensive linemen, its leading receiver (Corey Brown) and 1,500-yard rusher Carlos Hyde from last year's team.
Miller missed most of his senior season at high school in Huber Heights, Ohio, and has frequently been sidelined with injuries at Ohio State. As a freshman, he sprained an ankle against Nebraska -- a game in which the Buckeyes built a big lead but blew it -- but was able to play in subsequent games.
Two years ago, he missed time during the game at Michigan State when he fell into an equipment case on the sideline and later in the game hyperextended his left knee. He was hit hard by Purdue's Josh Johnson later in the season and missed the rest of that game, with Guiton leading a stirring march in the final minute for a touchdown and the tying two-point conversion. The Buckeyes won in overtime.
Last season, Miller sprained a knee early against San Diego State and missed the rest of that game and the next two, with Guiton filling in.
Then Miller partially tore the labrum in his right shoulder on the first possession against Clemson in the Orange Bowl. He played the rest of the game. When the injury was discovered later, he had surgery in February.
Ohio State said at the time that Miller had "minor, outpatient surgery." But he has had problems with the shoulder since.
Still, he has repeatedly said he would be ready to go in the opener and did so again between practices Monday. His workload had been reduced to avoid any ongoing soreness in the arm.
Miller has a $1 million total disability policy that he could collect if he never plays football again, a source told ESPN. That premium has been paid for by Ohio State, according to the source, but Miller does not have loss of value insurance that would cover him if he significantly slipped in the NFL draft.
ESPN.com's Austin Ward, ESPN's Darren Rovell and The Associated Press contributed to this report.