The Titans' defense figures to have whiplash trying to slow down Josh Allen after three weeks of facing Trevor Lawrence, Zach Wilson and a hobbled Carson Wentz. Similarly, Tennessee's offense hasn't faced a secondary near as cohesive and flexible as Buffalo's unit all year. While this game theoretically has letdown potential for the Bills after their big win in Kansas City, the Titans are worse than their 3-2 record indicates. I was surprised the Bills weren't favored by more because they've shown what they can do against mid-level competition.
Pick: Bills 33-21
This is one of those be-careful games for the Bills, who could be caught in a letdown after beating the Chiefs on the road Sunday night. The Titans beat the Bills last year by playing a lot of zone coverage to slow down the offense. But this Titans defense isn't very good. The Titans' offensive line also has issues. The Bills will win the game, but Derrick Henry will keep the Titans in it.
Pick: Bills 27, Titans 24
What to watch for: Something has to give. The Bills' defense is giving up 78.4 rushing yards per game, third best in the NFL. Tennessee's Derrick Henry is leading the league with 640 rushing yards and has four consecutive games with at least 100 yards on the ground. Henry had only 57 rushing yards in the Titans' 42-16 win over the Bills last season. -- Turron Davenport
Bold prediction: The Bills will limit Henry to his second game this year under 100 rushing yards and give the Titans' offense some issues. This season under defensive coordinator Leslie Frazier, the Bills have adapted to defending whatever offense is thrown at them. So while the Titans are averaging 167.8 rush yards per game this season (third most in the NFL), only three teams are giving up fewer yards per rush than the Bills' 3.7. -- Alaina Getzenberg
Stat to know: The Bills have scored 35-plus points in four straight games -- tied for the longest streak in franchise history. They could become the first team to score 35-plus points in five straight games since the Broncos in 2012-13.
Getzenberg's pick: Bills 35, Titans 24
Davenport's pick: Bills 35, Titans 31
FPI prediction: BUF, 72.4% (by an average of 8.2 points)
The Bills had an emotionally charged big win in Kansas City and will have a mild letdown against another AFC playoff team it has had some trouble against in the past. But Tennessee's offense doesn't have the firepower to keep up beyond the strong running of Derrick Henry. The Bills' passing game can beat the Titans in many areas downfield and they will have rushing success with Josh Allen and others, too.
Pick: Bills win 27-23
The Bills' defense ranks first in turnovers (15), second in passing yards allowed (867) and third in rushing yards allowed (392), showing it can carry its weight while Josh Allen and the offense have their fun. That's trouble for the Titans (3-2), who lean heavily on running back Derrick Henry, the league's leading rusher. It's unclear whether Titans receiver Julio Jones (hamstring) will return after missing two straight games, though he practiced Wednesday. The Bills (4-1) demolished Kansas City and are, along with the Ravens and Chargers, fighting for control of the A.F.C. bet accordingly.
Pick: Bills -6