The entered their bye week in NFL Week 13 with a six-game winning streak and a 9-2 record.
They are for Sunday Night Football, a team that struggled with several injuries to key players over the course of the season.
The Niners could be without stars like quarterback Brock Purdy, offensive tackle Trent Williams and defensive end Nick Bosa.
While their team is desperate for a win, a Buffalo victory could make history for the franchise.
In more ways than one.
The Bills are four games ahead of the AFC East runner-up and division rival Miami Dolphins, who will play the Green Bay Packers at Lambeau Field on Thanksgiving Thursday. Buffalo prevailed against them in both direct duels this season and is in the tiebreaker.
If Miami loses to Green Bay and Buffalo beats San Francisco, the Bills will also win their fifth straight division title.
This has never been achieved since the team was founded in 1960.
The franchise notably won four straight AFC East titles from 1988 to 1991, the last two of which included trips to the Super Bowl.
This is also worth mentioning . And while a win is never completely guaranteed, the team has a good track record in this situation.
However, that and their current regular season winning streak aren't the only ones at stake. Buffalo has also won six straight games against San Francisco.
QB Josh Allen will also have a chance to make more history in this game against a team he grew up rooting for in Firebaugh, California.
Allen is currently tied with the Bills' most famous quarterback in team history, Jim Kelly, for the most touchdowns in franchise history (244).
Josh Allen is tied with Jim Kelly for the most touchdowns in Bills history with 244. All he needs is 1 touchdown to break the record. Very good chance that we will witness history on Sunday evening…
— BillsMuse (@BillsMusee)
Per tankathonBuffalo has the fifth-easiest remaining schedule in the league this season, meaning Allen will have plenty of time in the remaining six regular-season contests to add to that number as he enters his prime at age 28.
He will also have a chance to cap off a strong campaign and a potential MVP-caliber year, just as the Bills will have a chance to play against the Niners for the No. 1 seed and a bye in the first round of the AFC Playoffs apply , Rams, Lions, Patriots (twice) and Jets.
