After a thrilling Opening Night, the 2025-26 NBA schedule continues with 12 games on Wednesday. Notable matchups on the Wednesday NBA slate include Cavaliers (-1.5, 228.5) vs. Knicks in a matchup of top Eastern Conference contenders, 76ers vs. Celtics (-3.5, 229.5) in a battle between longtime rivals, and Spurs vs. Mavericks (-2.5, 224.5) in a showdown between rising stars Victor Wembanyama and Cooper Flagg. Perennial All-Star candidates Jayson Tatum (Achilles) and Kyrie Irving (knee) will miss most, if not all, of the 2025-26 NBA season.
With 12 games listed in the latest NBA odds, there are coutless opportunities to build NBA parlays on Wednesday. What are the best NBA bets on the board? Who should you fade? Before locking in any NBA picks, you’ll want to see the NBA predictions and betting advice from SportsLine’s proven computer model.
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The SportsLine Projection Model simulates every NBA game 10,000 times and has returned well over $10,000 in betting profit for $100 players on its top-rated NBA picks over the past seven seasons. The model enters the 2025-26 NBA season on a sizzling 160-118 roll on all top-rated NBA picks, returning nearly $4,000. It also went 24-11 (69%) on top-rated NBA against-the-spread picks last season. Anyone following its NBA betting advice at sportsbooks and on betting apps could have seen huge returns.
Now, the model has scoured the latest NBA odds and locked in three confident NBA best bets. If you successfully parlay its picks, you’d be looking at a payout of well over +500. You can only see the model’s NBA picks at SportsLine.
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Top NBA picks for Wednesday, October 22
After simulating every game 10,000 times, the model is backing the Dallas Mavericks to cover (-2.5) against the San Antonio Spurs in the season opener for both teams at 9:30 p.m. ET. Dallas will be at home at American Airlines Arena for this matchup, which has an Over/Under of 224.5 points. The Mavs will be without All-Star guard Kyrie Irving, who is recovering from a torn ACL suffered last season, but they still boast one of the NBA’s most talented rosters.
Dallas has a projected starting lineup of D’Angelo Russell, Klay Thompson, Cooper Flagg, Anthony Davis, and Dereck Lively II. The Spurs are also talented, but young, and will be led by All-Star center Victor Wembanyama. All said, the model has the Mavericks covering the spread in 67% of computer simulations, making this a strong play for Wednesday. See which other NBA parlay picks to make here, and bet this pick right here:
How to make NBA predictions for Wednesday, October 22
The model also locked in a spread pick for both games, and it says one team covers almost 70% of the time in an A-rated pick. You can only see the model’s Wednesday NBA parlay at SportsLine.
What are the model’s top NBA parlay picks for Wednesday, and which best bets should you target for a chance at a payout of well over +500? Visit SportsLine now to see NBA best bets from a model that’s returned more than $4,000 on top-rated picks, and find out.
