A rare third meeting between Buffalo and New England will settle the score between the two AFC East rivals as the third-seeded Bills host the sixth-seeded Patriots in an AFC wild-card matchup on Saturday night in Orchard Park, N.Y.

The Bills opened as 4.5-point favorites at DraftKings and BetMGM,where the line has moved to 4.0 points with the action split and Buffalo backed by a slight margin at 52 percent of the spread-line money. Meanwhile, Buffalo has been backed by 60 percent of the bets and 65 percent of the money at DraftKings.

After splitting their two regular season meetings, the Bills and Patriots are set to meet in the playoffs for the first time since Dec. 28, 1963. Back then, a Boston Patriots team overcame the Bills 26-8 at War Memorial Stadium in Buffalo in a divisional round matchup.

"Playing at home in the divisional round against our division rival -- a team that's been the standard for long-term success in the NFL for the last 25, 30 years -- it's going to be a great challenge," Bills quarterback Josh Allen said. "It's going to be another dogfight."

New England has dominated the all-times series with Buffalo, posting a 77-46-1 record. In Buffalo, the Patriots are 38-23-1 and have gone 31-17 at the Bills' current venue of Highmark Stadium.

However, the departure of Patriots star quarterback Tom Brady has opened a window for the Bills. Buffalo ended New England's 11-year reign as AFC East champions one year ago as the Patriots finished 7-9 in their first season without Brady.

This year, a revamped New England team bounced back to make the playoffs for the 12th time in 13 seasons after finishing 10-7.

Yet even finding Brady's successor in former Alabama champion quarterback Mac Jones and a nearly $200 million free agent spending spree wasn't enough to keep the Bills from a second straight division crown after an 11-6 season.

Buffalo ended the regular season with four consecutive victories while New England limped to the finish line with three losses in its final four contests.

"Regardless of what level you're playing on, you understand what's at stake (in the playoffs)," Jones said. "We know the Bills are a really good team, they have a great defense -- top in the league -- and we understand that they have great players."

On the heels of its first AFC East title since 1995 last season, Buffalo forged a deep playoff run with a narrow win over Indianapolis in the wild-card round and a statement victory against Baltimore in the divisional round before ultimately falling short at Kansas City in the AFC Championship Game.

This season, the Patriots and Bills each took different routes to winning on the others' home field.

On Dec. 6, New England used an unorthodox and weather-altered game plan to win at Buffalo 14-10 in snowy and windy conditions. Jones attempted a franchise-record-low three passes and totaled 19 yards as Damien Harris' 111 rushing yards paced the Patriots' powerful run game to a victory.

In the rematch on Dec. 26 in Foxborough, Mass., Allen got his revenge after completing 30 of 47 passes for 314 yards and three touchdowns in Buffalo's 33-21 triumph. With their receiving corps depleted, lesser known wideout Isaiah McKenzie had a breakout performance for the Bills with 11 catches for 125 yards and a touchdown.

Conditions for the completion of this season's trilogy between the teams appear more likely to be similar to those of the first meeting in Buffalo. Forecasts are calling for bitter cold temperatures in the single digits at the time of kickoff.

New England starting left tackle Isaiah Wynn (hip/ankle) was ruled out on Friday. He could be replaced by Yodny Cajuste, who has two starts among seven career appearances. But their options to replace Wynn also include veteran Trent Brown, who's been starting at right tackle, and second-year lineman Michael Onwenu, who has played both guard and tackle.

Several other key New England players remain questionable for the game, including center David Andrews (shoulder), defensive lineman Christian Barmore (knee), linebacker Jamie Collins (ankle), kicker Nick Folk (knee in non-kicking leg), running back Damien Harris (hamstring) and linebacker Dont'a Hightower (knee).

The Bills are largely healthy, with wide receiver Emmanuel Sanders (knee) able to practice fully all week.