49ers vs. Colts Best NFL Prop Bets for Monday Night Football in Week 16 (Bet on Jonathan Taylor)

Breaking down the best prop bets for the San Francisco 49ers-Indianapolis Colts matchup in Week 16.

Indianapolis Colts running back Jonathan Taylor is a great prop target in Week 16. / Matt Pendleton-Imagn Images

A pair of Offensive Player of the Year candidates face off on Monday Night Football in Week 16, as Christian McCaffrey and the San Francisco 49ers hit the road to play Jonathan Taylor and the Indianapolis Colts.

The two star running backs are always intriguing player prop targets, and this matchup has a ton at stake in the playoff race for both teams, as the Colts are trying to get back into the mix in the AFC while San Francisco would love to remain in play for the NFC West division crown. 

Outside of Taylor and CMC, there are a ton of players to consider in the prop market in this matchup, including Brock Purdy, who has led the 49ers to four wins in a row since he returned from a toe injury.

As for the Colts, their passing game may be tougher to trust with 44-year-old Philip Rivers making just his second start since 2020 (!!) in this primetime matchup.

I’ve narrowed things down to my three favorite prop plays, so let’s examine each – and the latest odds – for this Monday night battle.

Best NFL Prop Bets for 49ers vs. Colts

Odds via BetMGM Sportsbook.

• Jonathan Taylor OVER 98.5 Rushing Yards (-115)
• George Kittle OVER 59.5 Receiving Yards (-118)
• Brock Purdy OVER 1.5 Passing Touchdowns (-172)

Jonathan Taylor OVER 98.5 Rushing Yards (-115)

Taylor enters Week 16 at No. 2 in the odds to win Offensive Player of the Year, and he’s in a good spot to have a big game on the ground against this San Francisco defense.

The 49ers rank 21st in the NFL in EPA/Rush, which is a far cry from the Seattle Seahawks (No. 1 in EPA/Rush), who Taylor faced last week. In that game, Taylor picked up 87 yards on 25 carries, showing that he’s going to handle a major workload with Rivers under center.

Taylor has 99 or more rushing yards in just five games this season, but he’s handled 21 or more carries in each of his last three games. 

That increased workload should go a long way for the Colts star, especially since San Francisco is allowing 4.3 yards per carry this season. 

George Kittle OVER 59.5 Receiving Yards (-118)

This is a great matchup for George Kittle, who has five straight games with 67 or more receiving yards.

The Colts have given up the fifth-most receiving yards to tight ends (928) this season and the sixth-most receptions (86).

Kittle has easily cleared this line in each of Purdy’s last four starts, and he should be the focal part of the 49ers passing game on Monday. Since Purdy returned, Kittle has been targeted 30 times in four games.

He should torch this Indy secondary that has dealt with a bunch of injuries in 2025. 

Brock Purdy OVER 1.5 Passing Touchdowns (-172)

In six starts this season, Purdy has thrown 12 touchdowns, throwing for multiple scores in four of his appearances.

He’s coming off a great game against the Tennessee Titans, throwing for 295 yards, three scores and no picks to lead the 49ers to their 10th win of the campaign. 

While Indy isn’t nearly as bad defensively as Tennessee, it has allowed the second-most passing yards in the NFL this year. So, I expect the 49ers to attack through the air quite often in this matchup. 

I like Purdy to find the end zone twice with his arm, as he’s used Christian McCaffrey as a receiver quite often in his starts. The 49ers quarterback seems to be playing more at the level that he did in 2023 when he threw for 31 scores in 16 games.

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Odds refresh periodically and are subject to change.

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