Week 10 NFL picks, best bets from proven model: This 5-leg parlay returns over 20-1

The San Francisco 49ers look to move to 8-1 on the season and 5-1 in the conference when they battle the Dallas Cowboys in a key NFC matchup on Sunday afternoon. The 49ers enter as 4.5-point favorites despite being bitten hard by the injury bug this season, which played a part in them adding Keenan Allen at the trade deadline. In another key game involving NFC West teams, the Rams take on the Cardinals (+9.5) as Los Angeles looks to stay in the hunt for the division crown without Puka Nacua (knee), and Arizona will start rookie Carson Beck.

There are a number of other intriguing matchups in Week 10, including several divisional matchups. Among them include Bills vs. Jets (+7.5), Panthers vs. Saints (-2.5), Jaguars vs. Titans (+10.5), Vikings vs. Packers (-3) and Steelers vs. Bengals (-3.5) on 'Sunday Night Football.' Before locking in any Week 10 NFL picks, be sure to see the NFL parlay and betting advice from SportsLine's proven computer model.

The model, which simulates every NFL game 10,000 times, is up more than $5,000 for $100 players on betting sites on top-rated NFL picks since its inception. The model entered Week 10 of the 2026 NFL season on a 62-52 run on top-rated picks dating back to 2024. Anybody following its picks at NFL betting sites could have seen strong returns.

Now, the model has scoured the Week 10 NFL odds and locked in five confident NFL best bets. If you successfully parlay its picks, you'd be looking at a massive payout of over +2000. You can only see the model's Week 10 NFL picks at SportsLine.

Top Week 10 NFL picks

After simulating every game 10,000 times, the model is backing the Over 37.5 in the Dolphins vs. Colts matchup, hitting in 56% of simulations at betting apps on Sunday at 1 p.m. ET. The Over has hit in three of the past four Miami games, and in six of the last 10 Indianapolis matchups. The Colts defense is ranked 30th in the league, allowing 27.7 points per game. The Dolphins' defense has given up 25 points per game, which is No. 22.

Both teams limp into this matchup with some pieces missing on offense. The Colts traded Quenton Nelson, Josh Downs and Keenan Allen, while the Dolphins are turning to Kyle McCord at quarterback with Malik Willis (groin) heading to the IR. Both teams still have a capable running back to work around, however, with Ollie Gordon II leading Miami's rushing attack, while Jonathan Taylor remained in Indianapolis despite some trade rumors.

Though both offenses have concerns, the weaknesses of the opposing defenses still has the model projecting 42 combined points. See which other NFL parlay picks to make here.

How to make Week 10 NFL parlays

The model also jumped on four other NFL matchups where it says the line is way off, including backing multiple spread picks that hit well over 50% of the time. You can only see the model's Week 10 NFL best bets and NFL parlay at SportsLine.