Manning had been recovering from neck surgery in May, the second such procedure in the past two years, and was ruled out for Sunday's season opener at Houston. It's the first time in his 227-game career Manning won't play.
His recovery, dependent on regeneration of nerves in the neck, was going slower than expected. That helped necessitate Thursday's operation, which carries a minimum recovery time of 2-3 months.
But his exact timetable for a return still isn't known. ESPN reported Manning planned to have a procedure similar to the previous two to alleviate pressure in his right arm but opted for fusion surgery on Thursday morning. No decision will be made on whether Manning is placed on injured reserve immediately.
Manning signed a five-year, $90 million contract in July. The Colts expected he might be limited in training camp, but did not foresee an extended absence or additional surgery. Manning is due a $28 million option bonus in the first week of the 2012 league year in March. What seemed like a foregone conclusion when the deal was signed is no longer automatic.
Colts owner Jim Irsay offered a bit of insight via Twitter earlier Thursday before news of the operation spread, saying "NFL Season opens 2nite!We had a good practice yesterday and r guys r fired up 4 the season.#18's out for awhile,but compete,we will/BELIEVE."
Manning has repeated publicly that he felt he was saddled by the lockout, which prevented him from rehabbing with the Colts' medical and training staff as contact with any team officials was strictly prohibited during the work stoppage.
Manning was activated from the physically unable to perform list last week and was expected to participate in limited, scripted portions of practice. But he was unable to work regularly.
Manning issued a statement Wednesday when the team announced he had been ruled out against the Texans.
"To say I am disappointed in not being able to play is an understatement. The best part about football is being out there on the field playing with my teammates," Manning said. "It will be tough not to be out there playing for the organization and our fans. I simply am not healthy enough to play, and I am doing everything I can to get my health back. The team will do fine without me, and I know for sure that I will miss them much more than they will miss me."
Manning signed a five-year, $90 million contract on July 30. Without their mainstay under center, the Colts scrambled to find a veteran to challenge Curtis Painter for the starting spot. They signed retired quarterback Kerry Collins on Aug. 24. Collins started seven games for the Titans last season but retired in July.
Collins, 38, was drafted by current Colts vice chairman Bill Polian and the Carolina Panthers with the No. 5 overall pick in the 1995 draft.