The former Florida State quarterback was selected by the AFC East side with the 16th pick at this year's NFL Draft.
Head coach Doug Marrone told the Bills' website: "I remember when I first got the job here in Buffalo, and I had been up here and played up here before, and I got out of the car in January and the wind I was like, wow. I never realised how windy it was that time of the year.
"We went back and researched all the teams that played in the North-East in the bad weather and all the success they had with quarterbacks and the common traits that they had.
"They were big and had big hands and were able to throw the ball in tough weather and that's what we were looking at."
Manuel had the largest hands of any quarterback in this year's Draft.