With the right game plan, that opportunity could be realized.
The Bills have been one of the league's best units in the offensive trenches, and they've found a rhythm on that side of the ball after struggling in Week 1.
Defensively, though, the Bills could be in for a long day. They haven't pressured opposing quarterbacks with a great deal of consistency, and Brady has only been pressured on 23.6 percent of his drop-backs this year, according to Pro Football Focus.
What exactly can the Bills do to pick up their second win over the Patriots in three tries?
Capitalize on Slow-Starting New England Offense
The Patriots' opening drives in the first three games have ended as such: punt, interception, punt.
The opening drives for Bills opponents have ended as such: interception, punt, punt.
The strategy didn't work out well for the Bills the first time around, but that was because Fitzpatrick threw an interception. By the Chiefs' fourth possession, which came 2:31 into the second quarter, they were already behind by 14 points. The Bills built a two-touchdown lead on the Browns by the time Cleveland possessed the ball for the third time, just 9:56 into the game.
Buffalo's ability to start hot on defense, while complementing that with a hot start on offense, has allowed it to run away with its previous two games.
Meanwhile, the Patriots' slow-starting offense doomed them against the Cardinals and nearly doomed them the week prior against the Titans (until a defensive play swung the game). The Patriots only scored three points on their first two drives against the Ravens before being awarded beautiful field position after an interception gave them the ball at the Ravens' six-yard line.
The Bills were unable to capitalize on the early miscue by the Jets, and because of their own mistake, they wound up in a hole they couldn't dig themselves out of. They've been much better about cashing in on those opportunities early in the past two weeks and have two wins to show for it.
They can pick up a third win in a row if they're able to do the same against the Patriots. That is, of course, if their offense comes out slow.
The Bills run a very vanilla defensive scheme, rushing only their four down linemen on almost every down. They have blitzed 22 times on 123 drop-backs (17.89 percent of the time) through three weeks, according to Pro Football Focus.
NFL Network's Michael Lombardi called the Bills' Cover 1 scheme a "high school defense." It didn't work against Mark Sanchez, and Brady will eat up those vanilla coverages faster than a kid eats vanilla ice cream.
Ow, brain freeze.
Take Advantage of Great Protection
If there's one thing the Bills have done consistently well all season, it's blocking up front.
Through three games, the Bills have the league's lowest sack percentage and have given up just one sack against the Jets, Chiefs and Browns. The Patriots pass rush was downright anemic against the Ravens, pressuring quarterback Joe Flacco on 11 of his 40 drop-backs (27.5 percent), according to Pro Football Focus.
Fitzpatrick, on the other hand, has been pressured on just 24.7 percent of his passes this season for the fourth-lowest pressure percentage, according to PFF.
This 3rd-and-6 play early on in the Bills' 24-14 win over the Browns came following a seven-yard completion to Stevie Johnson on 2nd-and-13.
This play was essential to the outcome of the game because the Bills would go on to score a touchdown just three plays later.
The routes took a long time to develop, except for Donald Jones' underneath route. Thus, the protection was necessary.
Fitzpatrick got exactly what he needed from his offensive line and had enough time to go through his progressions. He wisely held safety T.J. Ward in the middle of the field, allowing wide receiver Stevie Johnson to get open against man coverage.
The two connected and picked up 18 yards in the process.
He had a great pocket every time he stepped back to throw, while the Bills picked up two quick scores that forever changed the complexion of the game.
This 2nd-and-6 play after the first touchdown put a lot of pressure on the Bills offensive line. They are lined up in an empty set with no tight end help, once again with a play that would take a few seconds to develop.
The Bills offensive line rose to the challenge, though, allowing the play enough time to develop and allowing Fitzpatrick time to make the read and find an open Donald Jones for a big 17-yard gain to move the chains.
It looked like Johnson was the first read on the play, but he was double-teamed (circled in orange) while Jones broke free uncovered through the secondary and was brought down shortly after the catch by Browns safety Usama Young.
Giving any quarterback that much time in the pocket will help him play a lot better, but this is especially true for Fitzpatrick. Because the Bills offense lacks top-tier weapons in the passing game, the protection allows him more time to find his open man. Because he is still average at reading coverage, the protection allows him more time to do that, as well.
But most importantly are his throwing mechanics, which were a work in progress this offseason. Because of the protection in front of him, he has rarely reverted to his old throwing style and has taken well to the teaching of quarterback coach David Lee.
Erik Frenz is the AFC East lead blogger for Bleacher Report. Be sure to follow Erik on Twitter and "like" the AFC East blog on Facebook to keep up with all the updates. Unless specified otherwise, all quotes are obtained firsthand.