Bills vs. Jaguars odds, prediction, time: NFL picks, Monday Night Football bets by model on 41-22-run

SportsLine's model simulated Buffalo Bills vs. Jacksonville Jaguars on Monday Night Football 10,000 times

Teams trending in opposite directions will meet in the first of two Monday Night Football games when the winless Jacksonville Jaguars battle the unbeaten Buffalo Bills. Jacksonville opened the season with a 20-17 loss at Miami and an 18-13 home loss to Cleveland. Buffalo defeated Arizona, 34-28, in Week 1 and followed that up with a 31-10 win at Miami. The Jaguars, who reached the postseason two years ago, are looking to improve on last year's 9-8 mark and second-place finish in the AFC South. The Bills, who have reached the playoffs in six of seven seasons, including five in a row, are seeking their fifth consecutive AFC East title.

Kickoff from Highmark Stadium in Orchard Park, N.Y., is set for 7:30 p.m. ET. The Bills are 5.5-point favorites in the latest Jaguars vs. Bills odds, while the over/under for total points scored is 45.5. Before making any Bills vs. Jaguars picks, be sure to see the NFL predictions and betting advice from SportsLine's proven computer model.

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on top-rated NFL picks since its inception. The model enters Week 3 of the 2024 NFL season on an incredible 187-130 run on top-rated NFL picks that dates back to the 2017 season. It is also on a 41-22 roll on top-rated NFL picks since Week 7 of 2022.

The model also ranked in the top 10 on NFLPickWatch four of the past six years on straight-up NFL picks and beat more than 94% of CBS Sports Football Pick'em players four times during that span. Anyone who has followed it is way up.    

Now, the model has set its sights on Jaguars vs. Bills and just locked in its picks and NFL predictions. You can head to SportsLine now to see the model's picks. Here are several NFL odds and NFL betting lines for the spread, money line and over/under for Bills vs. Jaguars: 

• Jaguars vs. Bills spread: Buffalo -5.5
• Jaguars vs. Bills over-under: 45.5 points
• Jaguars vs. Bills money line: Buffalo -250, Jacksonville +203
• JAC: Jaguars have covered the third-quarter spread in 12 of their last 17 games (+6.75 units)
• BUF: Bills have hit the third-quarter money line in 11 of their last 19 games
• Jaguars vs. Bills picks: See picks at SportsLine

Why you should back the Bills

Quarterback Josh Allen, a first-round pick in the 2018 NFL Draft, is off to another solid start to his season. Through two games, he has thrown for 371 yards and three touchdowns on 31 of 42 passing, and has compiled a 124.2 rating. He has also carried 11 times for 41 yards and two scores. In parts of seven seasons, Allen has thrown for 23,074 yards, completing 63.4% of his passes, and has thrown for 170 touchdowns and just 78 interceptions for a 92.7 rating.

Also helping power the Buffalo offense is running back James Cook. He leads the team in rushing, carrying 30 times for 149 yards (5.0 average) and two touchdowns. He has eight first-down conversions and has a long run of 49 yards. In the passing attack, Cook has caught four passes for 49 yards (12.3 average) and one touchdown. In three seasons with the Bills, he has 356 rushes for 1,778 yards (5.0 average) and six touchdowns. See which team to pick here.

Why you should back the Jaguars

Wide receiver Gabe Davis aims for his third game in a row with 40-plus receiving yards. He also has 55 or more receiving yards in two of his past three games in prime time. Davis totaled 163 catches for 2,730 yards and 27 touchdowns over four seasons with Buffalo from 2020 to 2023. He has six catches for 105 yards (17.5 average) and five first-down conversions on the year.

Wide receiver Christian Kirk has four or more catches in four of his past five road games. In his last meeting against Buffalo, he had six catches for 78 yards. Under the lights, Kirk has played well. He has 90-plus receiving yards and a touchdown catch in two of his past three games in prime time. He also has 85-plus receiving yards in two of his three career games on Monday Night Football. See which team to pick here.

How to make Jaguars vs. Bills picks

SportsLine's model is leaning Over on the total, projecting 50 combined points. It has also generated an against-the-spread pick that hits in over 60% of simulations. You can only get the NFL model's picks at SportsLine.

So who wins Jaguars vs. Bills on Monday Night Football, and which side of the spread cashes in more than 60% of simulations? Visit SportsLine now to see which side of the Jaguars vs. Bills spread to jump on, all from the advanced model that is up well over $7,000 on its NFL picks, and find out.