Manuel underwent minor knee surgery midway through last month, putting his availability for the match against the New England Patriots in serious doubt.
The Bills also lost second-choice quarterback Kevin Kolb to a season-ending injury during the warm-up campaign, leaving undrafted rookie Jeff Tuel as the next in line to start the opening match of the season should Manuel not recover in time.
However, coach Doug Marrone insists that the 23-year-old is now "110%" fit and admitted that he had prayed for the rookie to recover in time.
"He's 110% healthy. He looks good out there. So that's what we're going to go with. When he first came back, I was like 'Wow, he looks pretty good,'. Then the thing was to be smart about it. When it started to move up, I started to feel like this was the way we were going," Marrone is quoted as saying by ESPN.
"What I was trying to make sure of was, by putting him back there, was there any chance [for it] to get worse? Once that was taken out of the equation, I felt very comfortable with the situation.
"Being Catholic, there was a lot of prayers. Honestly, you go home and say, 'I hope he's healthy, I hope he's healthy.' But you really don't know."
The Bills finished bottom of the AFC East last season and will be hoping to improve upon that in the upcoming campaign.