Cavaliers vs. 76ers Prediction, Odds and Best NBA Prop Bets for Thursday, Oct. 22

The new-look Philadelphia 76ers are 1-0 in the 2026-27 season, and they head home for LeBron James’ first game in front of the Philadelphia crowd as a member of the team on Thursday night.

Philly takes on the Cleveland Cavaliers and Donovan Mitchell, a team that made the Eastern Conference Finals last season and is making its debut in the 2026-27 season. Cleveland was a potential James landing spot in the offseason, and he obviously has a long history with the franchise, winning a title there in his second stint in the late 2010s.

The new-look Sixers starting lineup of James, Joel Embiid, Jaylen Brown, Tyrese Maxey and VJ Edgecombe was great in a win over the defending champion New York Knicks, and oddsmakers have them favored at home against the Cavs on Thursday night.

Cleveland added Peyton Watson in a sign-and-trade with Denver during the offseason, but it let multiple rotation players go – Dean Wade, Keon Ellis, Dennis Schroder, Max Strus – to bring Watson in. Mitchell, James Harden, Evan Mobley and Jarrett Allen are back, but are the Cavs good enough to win the East?

During the Mitchell era, Cleveland continues to come up short, and it’ll have an early measuring-stick game on the road against this Sixers team that expects to contend for a title in the East.

Let’s take a look at the latest odds, a player prop to bet and my prediction for Thursday’s matchup.

Cavaliers vs. 76ers Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

Cavs +2.5 (-110)
76ers -2.5 (-110)

Moneyline

Cavs: +114
76ers: -135

Total

235.5 (Over -105/Under -115)

Cavaliers vs. 76ers How to Watch

Date: Thursday, Oct. 22
Time: 7:00 p.m. EST
Venue: Xfinity Mobile Arena
How to Watch (TV): ESPN
Cavs record: 0-0
76ers record: 1-0

Cavaliers vs. 76ers Injury Reports

Cavs Injury Report

Nae'Qwan Tomlin -- out
Khalifa Diop -- out
Jarrett Allen -- questionable

76ers Injury Report

Tacko Fall -- out
Dominick Barlow -- out
Dean Wade -- questionable
Ariel Hukporti -- out

Cavaliers vs. 76ers Best NBA Prop Bet

76ers Best NBA Prop Bet

Tyrese Maxey OVER 2.5 3-Pointers (+106)

Earlier today, I shared in my NBA Best Bets column – Peter’s Points – why I love this prop for Maxey against Cleveland:

Maxey led the NBA in minutes per game in the 2025-26 season, and he played nearly 40 minutes on opening night in the Sixers’ win over the Knicks, taking 19 shots and nine 3-pointers in the process.

The star guard shot just 2-for-9 from beyond the arc, in the win, but he’s coming off three consecutive seasons where he averaged at least three made 3s on at least eight attempts per game. Maxey is a career 37.7 percent shooter from beyond the arc, so I expect his 3-point shooting to improve after a shaky performance on Tuesday.

A two-time All-Star, Maxey still finished with 28 points on Tuesday, and I love him against the Cavs and their shaky defense on Thursday. Peyton Watson won’t be able to guard every wing for this Philly team, and Maxey should be able to hunt Donovan Mitchell and James Harden all game long.

The Cavs also were a bottom-five team in opponent 3s made per game in the 2025-26 season. As long as the volume remains the same for Maxey, I think he’s undervalued at +106 to make three or more shots from deep in his second game of the season.

Cavaliers vs. 76ers Prediction and Pick

The Sixers looked fantastic on Tuesday night against the Knicks, and now they have a game under their belt heading into Thursday’s meeting with Cleveland.

The offense was a little sloppy for both Philly and New York in the opener, but the Sixers found a way to win despite a rough shooting night from beyond the arc. I think they’ll have a much easier time on offense against the Cavs, who finished in the middle of the pack in defensive rating last season.

I can’t say that I love Cleveland’s offseason, even though the Watson addition seems like a real win. The Cavs don’t have a ton of depth, and the team had a clear ceiling with James Harden on the team in the playoffs. Yet, the Cavs are running things back once again.

The Philly crowd should be awesome on Thursday with James and Brown making their home debuts, and I wouldn’t be shocked if the Cavs are the team with a little rust since this is their first game in the 2026-27 season.

I’ll simply take Philly to win and move to 2-0 after a strong showing in its season opener.

Pick: 76ers Moneyline (-135 at DraftKings)

Odds refresh periodically and are subject to change.

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Find Peter Dewey's NBA betting record here (futures included). You can also follow my daily plays on BetStamp here.

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