After an impressive season-opening win, the Philadelphia 76ers head into tonight's clash with the Cleveland Cavaliers as 59% favorites. Tip-off from Xfinity Mobile Arena is scheduled for 7 p.m. ET.
After showing terrific chemistry in the victory over New York, my Cavaliers vs. 76ers predictions expect Philly to keep the good times rolling against Cleveland.
Find out more in my NBA picks for Thursday, Oct. 22.
TOP PICK
Cavaliers vs 76ers prediction: 76ers moneyline
Play up to 63%.
I'm going with the moneyline because the Cleveland Cavaliers can keep this contest close. That said, the Philadelphia 76ers just beat the defending champion Knicks on banner night, with four starters finishing in double-digit scoring.
Philly also held New York to just 100 points. The Knicks scored only 85 points per 100 possessions with Joel Embiid on the floor, compared with 126 without him.
Cleveland center Jarrett Allen (knee) is questionable, and his absence would give Embiid a favorable matchup inside.
The Sixers' playmaking was also impressive, with four starters logging at least five assists. With their stars already showing chemistry, I like Philadelphia to win again at home.
COVERS INTEL: Cleveland allowed opponents to shoot 37.2% from three last season, while Philadelphia attempted 40 triples in its opener. That perimeter matchup supports the Sixers moneyline if they can find a rhythm from deep. 
Cavaliers vs 76ers combo
I'm eyeing two of Philly's stars to make their presence felt tonight.
Although Tyrese Maxey went just 2-for-9 from deep in the opener, the guard is a high-volume shooter who averaged 3.1 makes on 8.6 long-range attempts per game last season. The Cavs aren't great at defending the perimeter, and point guards averaged 2.7 threes against them in '25-26.
Embiid dished out six dimes against New York and averaged just below 3.5 assists per contest vs. Cleveland last season. The Sixers' starting five is showing solid chemistry, and with Embiid no longer the primary scoring focal point, I like him to have another productive night facilitating the offense and creating more open looks.
Cavaliers vs 76ers combo
- 76ers moneyline
- Tyrese Maxey Over 2.5 threes
- Joel Embiid Over 3.5 assists
Cavaliers vs 76ers player props
Cavaliers player prop: Donovan Mitchell Over 24.5 points (57%)
Play up to 61%.
Donovan Mitchell remains Cleveland's primary scoring option, and he was phenomenal against the Sixers last season. In four meetings, the former Louisville star averaged 27.8 points per game.
Spida is a three-level scorer who won't be fazed by Philly's defensive pressure. He always finds a way to score, and even with James Harden alongside him, Mitchell still showed out and had the highest usage rate. The guard averaged 26 points and 18.6 shot attempts per game with Harden as his backcourt mate.
76ers player prop: LeBron James Over 7.5 assists (55%)
Play up to 60%.
LeBron James had a smaller offensive role last season with the Lakers, and that will likely be the case again in Philly. That's why I like this prop for The King, who should be one of the 76ers' top playmakers as he looks to get Jaylen Brown, VJ Edgecombe, Maxey, and Embiid involved.
We saw Bron's vision at MSG, where he registered a team-high seven assists in 34 minutes. He finished the 2025-26 season averaging 7.2 dimes per game, ranking 17th in potential assists per game among players with at least 60 appearances.
Philadelphia shot below 30% from deep against New York, so better shooting could turn more of his passes into assists. With several proven scorers around him, I like James to reach eight assists.
- Top picks: 1-1, -0.89 units
- Combos: 0-2, -2.00 units
Cavaliers vs 76ers odds
For help understanding probabilities, see our odds calculator.
- Spread: Cavaliers +3.5 | 76ers -3.5
- Over/Under: Over 235.5 | Under 235.5
- Moneyline: Cavaliers 42% | 76ers 59%
For the full slate of NBA matchups, check out our NBA odds board!
Cavaliers vs 76ers trend
The 76ers have hit the moneyline in 25 of their last 45 games (+16.95 Units / 17% ROI). Find more NBA betting trends.
How to watch Cavaliers vs 76ers
| Location | Xfinity Mobile Arena, Philadelphia, Pa. |
| Date | Thursday, Oct. 22, 2026 |
| Tip off | 7 p.m. ET |
| TV | ESPN |
Cavaliers vs 76ers latest injuries
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