Indianapolis Colts vs. Buffalo Bills Betting Odds, Analysis, NFL Pick

The Buffalo Bills are 6-2 against the spread their last eight times out as underdogs, winning five of those contests outright. The Indianapolis Colts are 15-2 straight up and 12-3-2 ATS the last 17 times they've gone out as a favorite. So winning trends clash when the Bills and Colts, former longtime division rivals, renew acquaintances Sunday afternoon at Ralph Wilson Stadium.

Point spread: The Colts opened as 2.5-point favorites; the total was 48 early in the week, according to sportsbooks monitored by Odds Shark. (Line updates and matchup report)

NFL pick, via Odds Shark computer: 23.8-20.9 Colts

Why the Colts can cover the spread

Indianapolis is coming off a third straight 11-5 season and an AFC Championship Game appearance. The Colts also went 10-5-1 ATS last year, so they're now 33-15 SU and 29-17-2 ATS with Andrew Luck as their starting quarterback.

Indy ranked third in the league in total offense, 22nd in rushing, 11th in total defense and 18th against the run last season. But the Colts are also one of the best teams in the league at possessing the ball, ranking fifth last year in time of possession at plus-3:49 per game, and that's usually an excellent way to win games and cover spreads in the NFL.

Finally, since Luck's arrival, Indianapolis is 8-3-1 ATS as a favorite on the road, where the spreads are often more amenable.

Why the Bills can cover the spread

Buffalo is coming off a 9-7 season, after which it lost its head coach as Doug Marrone resigned. But fate took a hand, and the Bills ended up with defensive guru Rex Ryan, who inherits a pretty good situation.

Buffalo only ranked 26th in total offense and 25th in rushing last year, as injuries and poor quarterback play took their tolls, but defensively, the Bills ranked fourth overall and 11th against the run.

Buffalo will go with former Virginia Tech Hokie Tyrod Taylor at quarterback, and while he's inexperienced, his mobility may come in handy.

Smart pick

Buffalo may eventually find success with Ryan, but new regimes bring new systems, which take some time to sink in. Indianapolis, on the other hand, is a Super Bowl contender looking to get this season off to a winning start. The smart money here is on the Colts at the short spread.

Betting trends

The Colts are 7-1 SU in their last eight games against the Bills.

The total has gone under in the Colts' last five games on the road.

The Bills are 4-1 ATS in their last five games at home in September.

All point spread and lines data courtesy of Odds Shark, and all quotes gathered firsthand unless otherwise noted. Check out Twitter for injury and line movement updates and get the free odds tracker app.