Colts vs Bills Preseason Picks and Predictions: Keenum Leads Buffalo to Start Preseason

After Buffalo announced Josh Allen wouldn't play, the line shifted, and Indianapolis become favorites. With tons of depth and a capable backup in Case Keenum, our NFL betting picks like the underdog Bills vs. the Colts.

Last Updated: Aug 13, 2022 12:58 PM ET Read Time: 4 min
Zack Moss Buffalo Bills NFL
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The Indianapolis Colts and the Buffalo Bills open their respective preseason slates when they meet at Highmark Stadium this afternoon.

The Colts are looking to wipe the bad taste from their mouths of an embarrassing Week 18 loss to the Jaguars that cost them a playoff berth. The Bills won the AFC East last season but were ultimately dispatched in the divisional round in overtime by the Kansas City Chiefs in an instant classic. 

Which AFC playoff hopeful will start their preseason with a victory? Find out in our free NFL picks and predictions for Colts vs. Bills on Saturday, August 13.

Colts vs Bills odds

This odds widget represents the best odds available for each betting market from regulated sportsbooks.

The spread has swung dramatically for this preseason clash. The Bills opened as -3.5 favorites, but are now underdogs of either +1.5 or +2, depending on where you look. The Over has been a popular wager, with the initial total of 34 being bet up to as high as 36, though most sites have the line at either 34.5 or 35. 

Use the live odds widget above to track any future line movements right up until kickoff and be sure to check out the full NFL odds before placing your bets.

Colts vs Bills predictions

Predictions made on 8/12/2022 at 2:00 p.m. ET.
Click on each prediction to jump to the full analysis.

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Colts vs Bills game info

Location: Highmark Stadium, Buffalo, NY
Date: Saturday, August 13, 2022
Kickoff: 4:00 p.m. ET
TV: CBS Sports

Colts at Bills betting preview


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Betting trend to know

The Over is 5-2 in the Bills’ last seven games. Find more NFL betting trends for Colts vs. Bills.

Colts vs Bills picks and predictions

Our side and total predictions are based upon our analysis of the line and total in this game. Our best bet is our favorite pick across all markets.

Spread analysis

Bills head coach Sean McDermott has ruled quarterback Josh Allen out of Buffalo’s preseason opener, but prospective Bills bettors shouldn’t be scared away. 

McDermott has won each of his last seven preseason games with the Bills, so he takes these exhibitions fairly seriously. Resting Allen would seem to contradict that, but he’s smart to prevent the possibility of an injury to his top signal caller.

Buffalo would not be the preseason Super Bowl favorites if it didn’t have a deep roster, and quarterback is not a position it’s thin at. Case Keenum is expected to get the bulk of the early snaps for the Bills in this one.

The 34-year-old Houston product has been carrying a clipboard for most of the last few seasons, but it wasn’t all that long ago that he went 11-3 under center with the Vikings in 2017. Keenum won both of his starts in relief of Baker Mayfield with the Browns last year, completing 65.3 percent of his passes for 6.4 yards per attempt with three touchdowns and only one interception. 

Bettors seem to be vastly overreacting to the Allen news, swinging the line five points. Now there appears to be plenty of value with the Bills, so contrarians should take their shot here.

Prediction: Bills +2 (-110 at DraftKings)

Over/Under analysis

While Keenum and the rest of the Bills' offense do their thing, Matt Ryan and company should be able to keep up early on. 

As head coach Frank Reich told reporters, the newest Colts quarterback will suit up for his team’s preseason opener. Bettors should expect Ryan to play “maybe a quarter, maybe a little less,” per Reich’s estimate.

Ryan regressed in 2021, authoring long-time lows in touchdowns (20) and yards per attempt (7.1) while tossing 12 interceptions. But the now 37-year-old signal caller was playing behind a woeful offensive line in Atlanta, and a change in scenery should help the Boston College product. Not having to face either Jordan Poyer or Tre’Davious White for Buffalo doesn’t hurt. 

Also providing assistance in this game could be Jonathan Taylor, who led the NFL in both total rushes (332) and rushing yards (1,811) last season.

The Under has been a popular play in recent preseasons, cashing 58.8 percent of the time since 2019. But the average line in that sample was 36.8 points. In Week 1 of this year’s preseason, the average line is 33.5, and games in that sample eclipsed that line 57.4 percent of the time. 

Prediction: Over 34.5 (-115 at Unibet)

Best bet

Don’t be concerned with Allen sitting out and back the Bills this Saturday. Allen missed each of his team’s first two preseason tilts last year, and Buffalo won both contests. 

If you blindly wagered on every NFL preseason underdog against the spread since 1995, you would have won 53.7 percent of the time or a +1.3 percent edge against the house based on all sides paying at -110. 

Buffalo is the better and deeper team overall, and it should show in front of its rowdy home fans on Saturday afternoon.

Pick: Bills +2 (-110 at DraftKings

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