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Philadelphia 76ers vs. Boston Celtics prediction, pick on Wednesday 10/22/25

Philadelphia 76ers vs. Boston Celtics prediction, pick on Wednesday 10/22/25

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By: Bryan Armetta

Two of the Eastern Conference’s biggest enigmas are set to meet tonight at TD Garden.

For the visiting 76ers, this season is all about health. If former All-Stars Joel Embiid and Paul George are playing, this is one of the more dangerous teams in basketball. That’s easier said than done, as both of these aging superstars have a worrying injury history. On the flip side, Boston will be without its best player following Jayson Tatum’s ACL tear last spring. In addition, the Celtics parted ways with several key contributors from their title-winning 2024 squad.

In this battle between historic rivals, who has the edge tonight? Here’s my preview, prediction, and pick for Wednesday’s season-opening Philadelphia 76ers vs. Boston Celtics matchup.

The Celtics are 4.5-point favorites (-105) over the 76ers on DraftKings Sportsbook. The total for this matchup is set at 229.5 points.

76ers vs. Celtics prediction, preview

As previously mentioned, the Celtics will look much different this season. Kristaps Porzingis, Jrue Holiday, Luke Kornet and Al Horford all left Beantown this summer. Their departures, in addition to Tatum’s injury, leaves Boston short-handed. This team’s success will likely hinge on the duo of Jaylen Brown and Derrick White. The former of the two averaged 22.2 points, 5.8 rebounds and 4.5 assists on 46/32/76 shooting splits last season. Brown will take on a much bigger role going forward, serving as an offensive hub for the C’s.

Boston does have enviable guard depth. Last season’s Sixth Man of the Year, Payton Pritchard, will now enter the starting lineup. One of the game’s best shooters, it’ll be interesting to see if the Oregon alum can maintain his elite efficiency. In addition, offseason pickup Anfernee Simons flashed some intriguing potential during the preseason. The former Trail Blazer could serve as a microwave scorer off the bench to start the year.

That’s the good news for the Celtics. Unfortunately, their front court is absolutely devoid of proven NBA talent. Right now, the 4 and 5 spots are divvied up among Neemias Queta, Sam Hauser, Chris Boucher and Luka Garza. None of those names should elicit much confidence. That’s especially true going into a matchup with Joel Embiid. The former MVP has been plagued by injuries in recent seasons. Still, when active, he’s a force to be reckoned with.

It’s not just down low where the Sixers have reason for optimism. Paul George (knee) is out, but fellow scorer Tyrese Maxey is capable of leading his club to a win. Last season, the guard served as Philly’s de facto top option on offense. Through 52 games, he averaged 26.3 points, 3.3 rebounds and 6.1 assists on 43.7% shooting (33.7 3PT%). The 24-year-old has scored at least 32 points in three of his previous four meetings with Boston.

76ers vs. Celtics pick, best bet

Everyone knows the 76ers are a massive injury risk. However, the team is somewhat healthy right now, especially by their own standards. In comparison, the Tatum-less Celtics lack the high-end depth that fans have grown accustomed to. In addition, Philadelphia’s defense is upgraded thanks to rookie V.J. Edgecombe. The wing could make things even more difficult on this three-point reliant Boston offense tonight. Given the talent expected to take the floor, I’ll back the visitors at plus money on Wednesday.

Best Bet: 76ers ML (+142)

Bryan Armetta is a New York-based writer that has spent over eight years in sports media. Working for DraftKings since 2024, he currently serves as a writer, editor and analyst for all things sports and pop culture. Bryan specializes in MLB, NBA, NFL, college sports and entertainment content. Prior to his time at DKN, he worked for MLB Network, NHL Network and SiriusXM Sports.
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I am a promoter at DraftKings and am also an avid fan and user and may sometimes play on my personal account in the games that I offer advice on. Although I have expressed my personal view on the games and strategies above, they do not necessarily reflect the view(s) of DraftKings and do not constitute a representation that any particular strategy will guarantee success. All customers should use their own skills and judgment in building lineups. I may also deploy different players and strategies than what I recommend above. I am not an employee of DraftKings and do not have access to any non-public information.