Christian McCaffrey, Jonathan Taylor And 3 More PrizePicks Plays For 49ers Vs. Colts

These are the five top PrizePicks plays for the 49ers-Colts clash on Monday Night Football to cap off Week 16.

Nov 30, 2025; Indianapolis, Indiana, USA; Indianapolis Colts running back Jonathan Taylor (28) warms up before a game against the Houston Texans at Lucas Oil Stadium. | Robert Goddin-Imagn Images

The San Francisco 49ers will go on the road to take on the Indianapolis Colts on Monday Night Football in Week 16. This highly implicated matchup will feature some of the most popular PrizePicks plays of the NFL’s Week 16 slate. Jonathan Taylor, Christian McCaffrey and other stars will have prominent roles in a must-win clash, presenting reason to believe in their MNF props. With both squads looking to secure a crucial win, here are the five top PrizePicks plays for Monday night’s showdown: 

Christian McCaffrey Over 62.5 Rushing Yards

Dec 14, 2025; Santa Clara, California, USA; San Francisco 49ers running back Christian McCaffrey (23) is tackled by Tennessee Titans safety Kendell Brooks (30) towards the end zone during the third quarter against the San Francisco 49ers at Levi's Stadium. | Kyle Terada-Imagn Images

It’s no secret that McCaffrey is one of the top dual-threat backs in the NFL, offering the 49ers’ offense immense versatility. Entering Week 16, the All-Pro back leads the team in both rushing and receiving yards, but could see more of a traditional role as a rusher on Monday night. Two stellar rushing offenses are slated to square off in prominent roles on MNF, with McCaffrey eclipsing 20 carries in each of his last three games. During that span, he’s averaging 71.6 rushing yards, a trend that projects to continue in Week 16. 

Jonathan Taylor Over 97.5 Rushing Yards

Dec 14, 2025; Seattle, Washington, USA; Indianapolis Colts running back Jonathan Taylor (28) rushes against the Seattle Seahawks during the second half at Lumen Field. | Kevin Ng-Imagn Images

Taylor’s rushing prop is a bold pick for Week 16 parlays, but his 97.5-yard mark might not be so absurd considering several factors. With Philip Rivers under center, Indianapolis has made its offensive identity clear. Matched up against one of the top defenses in the NFL in Week 15, Shane Steichen kept the ball on the ground, carving out 25 carries in the run game. Matched up against the 49ers’ defense, which has allowed 130 rushing yards in each of its last two games, the former OPOY projects to sustain his league-leading rushing campaign in primetime.

Alec Pierce Over 21.5 Receiving Yards

Indianapolis Colts wide receiver Alec Pierce (14) goes up to make a catch for a touchdown Sunday, Nov. 30, 2025, during a game against the Houston Texans at Lucas Oil Stadium in Indianapolis. | Christine Tannous/IndyStar / USA TODAY NETWORK via Imagn Images

Alec Pierce has emerged as the Colts’ leading receiver with a stellar trend of production this season. Indianapolis’ long-ball threat is leading the league in yards per catch entering Week 16, averaging 20.1 YPC on the year, nearly eclipsing his PrizePicks prop in just one catch on average. The Colts offense should find greater success through the air, matched up against the 23rd-ranked pass defense of San Francisco, which could help Pierce revert to his previous trend of output, posting 75 yards in each of his previous three games prior to Week 15. 

Ameer Abdullah Over 4.5 Receiving Yards

Dec 14, 2025; Seattle, Washington, USA; Indianapolis Colts running back Ameer Abdullah (26) returns a punt against the Seattle Seahawks during the third quarter at Lumen Field. | Kevin Ng-Imagn Images

Veteran running back Ameer Abdullah emerged as Indianapolis’ leading receiver in a quiet performance from the passing game. He hauled in each of his five targets for 32 yards in an expanded role, adding four carries for 15 yards on the ground. I’m a fan of Abdullah’s receiving play, considering his new role with Rivers under center, which should continue against an inconsistent San Francisco defense. 

George Kittle Over 6.0 Receptions

Dec 14, 2025; Santa Clara, California, USA; San Francisco 49ers tight end George Kittle (85) scores a touchdown during the third quarter against the Tennessee Titans at Levi's Stadium. | Cary Edmondson-Imagn Images

Following an extended absence earlier in the season, George Kittle has provided a valuable spark for the 49ers’ passing game. Over his last five games, Kittle has caught at least six passes four times, averaging 6.6 catches for 76.7 receiving yards during that span. The All-Pro tight end will remain a popular target for Brock Purdy, something that projects to continue in a must-win game for the 49ers.