2025 NFL Monday Night Football Week 16 Betting Lines
He won’t be the NFL’s MVP this season but the Indianapolis Colts are seeing just how important Daniel Jones was to their success. The Colts won eight of their first 10 games and had a nice lead in the AFC South until the roof caved in. Jones was lost for the season a few weeks in a loss to Jacksonville; one setback in the middle of four straight that has dropped Indy out of the AFC playoff picture. Backup Riley Leonard was also injured forcing the club to bring Philip Rivers out of retirement.
Rivers is expected to start when the Colts host the streaking San Francisco 49ers in the Week 16 edition of Monday Night Football. With four straight victories the Niners continue to put pressure on the Rams and Seahawks in the NFC West, arguably the toughest division in football with three teams winning at least 10 games and currently in a playoff spot. The game at Lucas Oil Stadium in Indianapolis, IN kicks off at 8:15 p.m. ET on Dec. 22 and will air on ABC and ESPN.
49ers at Colts MNF Week 16 Lines
Spread: 49ers -6
Total: 46.5
Money Line: 49ers -286, Colts +234
49ers at Colts Betting Preview
The 49ers have taken advantage of a soft spot in their schedule to stay within striking distance of first place in the NFC West. Their current 4-game winning streak came after a brutal 43-26 home loss to the Rams and included wins over Arizona, Carolina, Cleveland and Tennessee. None of those clubs has a winning record and they boast a combined ledger of 15-41.
The Niners are winning the games they need to and doing it handily. Each win during their current streak was by more than 10 points with an average margin of 15.3 points. That allowed them to go on a nice run at the betting window with payouts in all four contests. The Niners won and covered their last three road games and are 6-2 SU and ATS away from home this season.
The current run coincided with the return of Brock Purdy to the lineup. Purdy missed six of the first eight games of the season, but he’s healthy now leading a unit that’s averaged 31 points during the winning streak. Since returning Purdy has completed nearly 70 percent of his passes with eight TDs and three interceptions. All three picks came in the 20-9 win over Carolina in Week 12.
Despite the loss of top defenders Fred Warner and Nick Bosa earlier in the year the unit has held its own. During their winning streak they held two opponents to less than 10 points and for the season they are 10th in scoring defense and 18th in total defense. The Niners have played OVER the total seven times with a push in their past 11 games.
Not long ago the Colts led the NFL in scoring averaging more than 30 points. They failed to score more than 20 points using three different starting QBs in their last four games. And the Colts have turned to a 44-year-old just out of retirement to turn the offense, and the season, around. Rivers nearly did it last week in Seattle throwing a TD pass that gave Indy the lead. Overall, though, the offense was sedated in the 18-16 loss. Rivers had just 120 yards passing and the Colts amassed a season-low 215 yards.
The defense held up its end of the deal not allowing a TD and holding the Seahawks to 2 of 13 on third down plays. That allowed the Colts to stay within the 13-point spread for just their second payout in the last six games. They also played UNDER the total for the third time in their last four games. Moving forward the Colts will need to rely on a defense that’s been above average. The group gives up a lot of yards but keeps points off the board allowing an average of 21.6.
A majority of games between the clubs took place prior to the 1970 NFL/AFL merger with the teams clashing 34 times. This will be only the 12th meeting since 1970 with the Colts winning the last five and registering three consecutive payouts.
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2025 Monday Night Football Betting Schedule
| WEEK |
VISITING TEAM |
HOST TEAM |
SCORE |
| Week 1 |
Minnesota Vikings |
Chicago Bears |
27-24 |
| Week 2 |
Tampa Bay Buccaneers |
Houston Texans |
20-19 |
| Week 2 |
Los Angeles Chargers |
Las Vegas Raiders |
20-9 |
| Week 3 |
Detroit Lions |
Baltimore Ravens |
38-30 |
| Week 4 |
New York Jets |
Miami Dolphins |
21-27 |
| Week 4 |
Cincinnati Bengals |
Denver Broncos |
3-28 |
| Week 5 |
Kansas City Chiefs |
Jacksonville Jaguars |
28-31 |
| Week 6 |
Buffalo Bills |
Atlanta Falcons |
14-24 |
| Week 6 |
Chicago Bears |
Washington Commanders |
25-24 |
| Week 7 |
Tampa Bay Buccaneers |
Detroit Lions |
9-24 |
| Week 7 |
Houston Texans |
Seattle Seahawks |
19-27 |
| Week 8 |
Washington Commanders |
Kansas City Chiefs |
7-28 |
| Week 9 |
Arizona Cardinals |
Dallas Cowboys |
27-17 |
| Week 10 |
Philadelphia Eagles |
Green Bay Packers |
10-7 |
| Week 11 |
Dallas Cowboys |
Las Vegas Raiders |
33-16 |
| Week 12 |
Carolina Panthers |
San Francisco 49ers |
9-20 |
| Week 13 |
New York Giants |
New England Patriots |
15-33 |
| Week 14 |
Philadelphia Eagles |
Los Angeles Chargers |
19-22 |
| Week 15 |
Miami Dolphins |
Pittsburgh Steelers |
15-28 |
| Week 16 |
San Francisco 49ers |
Indianapolis Colts |
- |
| Week 17 |
Los Angeles Rams |
Atlanta Falcons |
- |
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