Week 16 of the NFL regular season concludes with a Monday Night Football matchup between the Indianapolis Colts and San Francisco 49ers. With the latter still looking to remain alive in the chase for an NFC West title — which could come down to the final week of the campaign — a win tonight on the road at Lucas Oil Stadium remains imperative for the Niners. Can Brock Purdy lead his team to glory?
Here are the best Brock Purdy prop bets for 49ers vs. Colts on Monday Night Football in Week 16.
Best Brock Purdy prop bets on DraftKings Sportsbook
Brock Purdy signed a massive five-year, $265 million contract over the offseason, rewarding the former Mr. Irrelevant for his excellent play under center for this 49ers team over the last couple of seasons. His 2025-26 campaign hasn’t played out quite as well as initially hoped for due to a turf toe injury which sidelined him for eight weeks, and he didn’t quite look like himself upon making his return, either. However, the quarterback put forth his best effort of the season last week with 295 yards and three touchdowns, showing that he may be back to his old ways.
In Week 16, Purdy gets a matchup against the Colts, who won’t have top cornerback Sauce Gardner available as the former All-Pro continues to manage a calf injury. With that in mind, the outlook appears quite solid for the San Francisco offense and its passing attack. Indianapolis allows 247.6 passing yards per game, third-most of any team, as well as 7.1 yards per pass, 17th overall. The Colts are also 15th in defensive EPA/pass, though they’ve allowed the fourth-fewest passing touchdowns with just 18 on the campaign. With this defense ranked 30th in PFF coverage grade, there are areas Purdy and the 49ers can target in this contest via the air.
On DraftKings Sportsbook, Purdy’s passing prop bet lines are set at O/U 33.5 pass attempts, 21.5 completions, 248.5 yards and 1.5 touchdowns. His rushing prop line sits at O/U 11.5 yards with +550 odds to score an anytime touchdown.
While the Colts’ tendency to allow lots of passing yards may stem from opponents playing catch-up for most of the season against what was one of the league’s top offenses, there’s still a very positive outlook for Purdy and his receiving weapons tonight. There have been seven occurrences of opposing quarterbacks throwing for at least 249 yards against the group over the 15-game sample, and Trevor Lawrence narrowly missed that line with 247 passing yards in Week 14. Over the last four weeks, Indianapolis allowed over 248.5 yards via the air three times and nearly did so again in that game against the Jaguars as well. We see opponents attack via the pass on a consistent basis, and with Christian McCaffrey running somewhat inconsistently and facing the NFL’s fourth-ranked rushing defense, we could see another pass-happy script here tonight.
With that in mind, Purdy should sling the ball plenty tonight. He’s eclipsed 248.5 passing yards in three of his six games this season and now enters this one coming off his best performance of the year. The confidence should be building for the quarterback, and given the must-win scenario to stay alive in the NFC West hunt, the 49ers will almost certainly come out aggressively tonight. I like the over here for sure.
Best Bet: Brock Purdy over 248.5 passing yards (-112)
Click the odds of this bet to tail!
