It's time for Monday Night Football and a look at the latest Titans vs Bills odds. 

The two squads got off to very different starts in Week 1. The Bills delivered a dominating win over the defending champion Los Angeles Rams, while the Titans coughed up a 13-point lead at home before losing to the New York Giants.

Can Tennessee turn the tides, or will Buffalo keep it rolling in Week 2?

Titans vs Bills odds

Per BetMGM

  • Betting Favorite: Bills (-9.5)
  • Moneyline odds: Titans +350, Bills -450
  • Point Total: 48.5 (over/under)
  • Location: Highmark Stadium, Orchard Park, NY
  • Time/Network: 7:15 PM EST on ESPN

After how they handled themselves during the season opener in Los Angeles – handing a 31-10 beating to the defending Super Bowl champion Rams – it's no surprise the Bills enter the second week of the season as heavy favorites.

The Titans, conversely, enter the week after losing 21-20 in one of the biggest stunners of opening weekend to the Giants.

Titans vs Bills Injury Report

The teams enter Week 2 with a combined 14 players on their injury report. Nine of these come from the Titans – including leading Week 1 receiver Kyle Phillips, starting left tackle Taylor Lewan and top cornerback Kristian Fulton. Dontrell Hilliard, who caught both of Ryan Tannehill's touchdown passes in Week 1, also finds himself on the list.

Titans Injury Report

  • CB Kristian Fulton (Hamstring)
  • RB Dontrell Hilliard (Hamstring)
  • WR Kyle Phillips (Shoulder)
  • OLB Ola Adeniyi (Neck)
  • C Ben Jones (Not Injury Related)
  • OT Jamarco Jones (Elbow)
  • OT Taylor Lewan (Knee)
  • CB Lonnie Johnson (Groin)
  • OT Dillon Radunz (Neck)

Bills Injury Report

  •  OT Tommy Doyle (Foot)
  •  CB Dane Jackson (Knee)
  • TE Quinton Morris (Hamstring)
  •  DT Ed Oliver (Ankle)
  •  DT Tim Settle (Calf)

The biggest name on the list for the Bills is cornerback Dane Jackson, who played nearly every defensive snap for the Bills in the opener. Defensive tackles Tim Settle and Ed Oliver are big names, but they played fewer defensive snaps combined in Los Angeles than fellow defensive tackle DaQuan Jones.

Titans vs Bills Head-to-Head

The teams played in each of the past four regular seasons and have the series split at 2-2, but the Titans won the two most recent games by a combined score of 76-47. 

While the oddsmakers have the point total at 48.5, both teams have scored over 20 points in only one of those last four meetings.

Here are some trends for Titans vs Bills betting odds from recent meetings: 

  • The home team is 3-1 ATS in their last four meetings
  • The over is 2-2 in their previous four meetings

NFL betting is all about finding an edge. Unfortunately, there isn't a ton in those meetings to lean into when making your Titans vs Bills picks.

Titans recent record on the road

This will be the Titans' first road game of 2022. Here's a look at how they performed a season ago:

Titans 2021 road trends

  • Straight up: 5-3
  • ATS: 4-4
  • ATS as a road underdog: 3-2

Bills recent record at Highmark

After a resounding season opener, Buffalo returns home in front of a raucous crowd. Here's a look at how they performed at Orchard Park last season:

Bills 2021 home trends:

  • Straight up: 7-3
  • ATS: 5-3-2
  • ATS as a home favorite: 5-3-2

Titans vs Bills Prediction

There's a lot to sift through in looking at Titans vs Bills odds.

The Bills came out like a house on fire in Week 1, and it's hard to imagine a drastic fall-off in their home opener. 

Josh Allen showcased why he is a leading MVP candidate, leading a Buffalo second-half scoring barrage. Can he capitalize against a Titans defense that conceded 21-second-half points to the Giants?

It wasn't all doom and gloom for the Tennessee D in Week 1. In fact, the Titans and Bills sacked the opposing quarterback a combined 12 times – the Bills tied the Chargers and Steelers for the highest sack total with 7, while the Titans tied the Chiefs for the fourth-highest total at 5.

The Bills had the league's top pass defense in 2021 but ranged more toward the middle of the pack against the run, allowing 112.5 per contest. That could give Derrick Henry enough daylight to help Tennessee move the ball and grind down the clock. 

Buffalo has more talent on both sides of the ball, but Tennesse is a battle-tested unit that won't get embarrassed in prime time.

Prediction: Tennessee +9.5

Props and value bets to watch:

Here are some other Titans vs Bills odds to consider:

  • Under 48.5 (-110)
  • Bills Double Result (-185) – to lead at the half and win outright
  • Gabe Davis anytime TD (+175)
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