SPREAD: Colts +7 | O/U: 50
The last seven weeks for the Colts have been building to this. They've fought back from an 0-3 record to .500 despite blowing two big leads and now need Carson Wentz to hold up against the league's most cohesive defense. That's asking too much, yet I think the underrated Colts defense is built to slow the Bills down, much like they did in the playoffs a year ago. A seven-point spread is too much for a Bills squad that, through no fault of its own, has few data points against quality opposition this year.
Pick: Bills 26-20
The Bills got back on track last week with a victory over the Jets, while the Colts edged the Jaguars. Buffalo's defense continues to play top-level football, as it allows just 3.8 yards per rush on the ground. That's a problem for Jonathan Taylor and the Colts offense. That will force Carson Wentz to win it, and he won't. Bills take it.
Pick: Bills 30, Colts 20
The Colts need to run well with Jonathan Taylor from wire to wire to get the rest of their offense rolling. The Bills' run defense can at least contain him early and put Carson Wentz in more uncomfortable situations in the elements on the road in November. Josh Allen will find plenty to exploit vs. the Colts' pass defense and his newfound patience will be an asset here. The Bills face limited Colts' weapons while the Colts can't account for all the skill around Allen.
Pick: Bills win 27-17 and cover the spread.
What to watch for: Can the Bills slow down Colts running back Jonathan Taylor? Buffalo's defense has limited opponent backs this season, with only one rushing for over 100 yards (Derrick Henry). Taylor has the most runs of 10-plus yards in the NFL, while the Bills are tied for the second-fewest long rushes allowed. Something has to bend. Overall this season, Buffalo's defense has overwhelmed opponents, averaging 15.0 points against per game (fewest in the NFL). Stopping Taylor will be a big test. -- Alaina Getzenberg
Bold prediction: Colts quarterback Carson Wentz will throw two interceptions against Buffalo. He has only three interceptions on the season, but the Bills have forced an NFL-high 24 turnovers, including 15 interceptions. Wentz, to his own acknowledgement, is a risk-taker when it comes to trying to make plays happen. The Bills, unlike other teams in the league, will make Wentz pay for taking those chances. -- Mike Wells
Stat to know: The Bills have outscored opponents by 145 points this season, and the best point differential through 10 games in franchise history is plus-138 (1990). They currently rank second in points per game (31.1) and first in points allowed per game (15.0), meaning they could become the first team since the 2007 Patriots to lead the NFL in both scoring offense and scoring defense in Week 11 or later.
Wells' pick: Bills 24, Colts 20
Getzenberg's pick: Bills 27, Colts 24
FPI prediction: BUF, 76.3% (by an average of 9.6 points)
MDS's take: The Bills' defense will shut Carson Wentzdown in a low-scoring game.
MDS's pick: Bills 13, Colts 10.
Florio's take: The Bills are moving in the right direction, but the Colts won't roll over. Just like they didn't roll over in the playoffs.
Florio's pick: Bills 24, Colts 17.
A win — no matter how ugly or close — is a win, and the Colts' (5-5) narrowly beating the lowly Jaguars last week kept their playoff hopes realistic in the wide-open A.F.C. The Bills (6-3), though, should bring them back to reality. Buffalo's top-ranked defense can frustrate Carson Wentz in ways the Jets and Jaguars didn't during the Colts' two-game winning streak, while Josh Allen relishes carving up the Colts' secondary, ranked seventh in passing yards allowed (2,499). Pick: