James, playing his first game in Cleveland since opting to head to Philadelphia as a free agent in June rather than returning for a third stint with his hometown Cavs, was greeted by warm cheers -- and scattered boos -- when he was introduced.
The four-time NBA champion, playing his 24th NBA season at the age of 41, was cheered again when he exited the game late in the fourth quarter.
In between it was a rough night for James and his Sixers teammates, who suffered just their second defeat of the young season.
The league's all-time leading scorer finished with eight points on three-of-12 shooting with seven rebounds, three assists, two steals and six turnovers.
Star center Joel Embiid missed all nine of his shots from the floor, making six free throws for six points.
Jaylen Brown, like James an off-season import, led the Sixers with 20 points, but the Cavaliers seized control early and repelled every Philadelphia surge to halt their two-game slide.
Donovan Mitchell scored 10 of his 23 points in the first quarter. Evan Mobley added 22 points, and Cleveland out-rebounded Philadelphia 56-42 despite the injury absence of center Jarrett Allen.
"I did not feel in a good rhythm offensively," James said. "We didn't look like much offensively. We had a couple of spurts. We were able to cut (the deficit) to three in the third quarter. But too many turnovers on my behalf."
Friday's games were part of NBA Cup group-stage action. The New York Knicks won the in-season tournament last year before going on to win their first NBA title since 1973.
Group-stage Cup games will be played throughout November, all counting in the regular-season standings. Quarter-finals will be played December 4-5 and semi-finals December 8-9 before the final on December 11 at Hinkle Fieldhouse in Indianapolis, Indiana.
The Boston Celtics drained a whopping 24 three-pointers on 44 attempts in a 119-80 blowout of the Hornets in Charlotte.
Jayson Tatum, back after sitting out Wednesday's win over the Bucks, drilled five three-pointers on the way to a game-high 34 points for Boston -- who led by as many as 46 points in the wire-to-wire win.
"I thought every shot he took was a great shot," Celtics coach Joe Mazzulla said of Tatum, who added eight rebounds and nine assists.
The Oklahoma City Thunder continued their dominance of the Grizzlies with a 128-97 win in Memphis.
Ajay Mitchell scored a career-high 35 points and two-time defending NBA Most Valuable Player Shai Gilgeous-Alexander added 28 for the Thunder, who notched a 13th straight regular-season win over the Grizzlies despite missing injured starters Jaylen Williams, Cason Wallace and Chet Holmgren.
The absences were irrelevant as the Thunder jumped to a 71-49 halftime lead. Memphis dropped their third straight defeat after opening the season with six straight wins.
In Dallas, Cooper Flagg and Kyrie Irving came alive in the second half to help the Mavericks beat the Utah Jazz 112-100.
Dallas forward P.J. Washington scored 22 of his 26 points in a first half that ended tied 57-57.
Flagg, who scored four points before the break, finished with 21 and Irving, held to two points in the first half, finished with 14 as Dallas used a big third quarter to gain control and held on down the stretch.
Around the League
Elsewhere, Alijah Martin and RJ Barrett both dropped 27 points for the Toronto Raptors as they rolled 121-107 over the struggling Milwaukee Bucks, with Tyler Herro once again leading the scoring with 23 while the rest of the team struggled mightily.
The Atlanta Hawks moved to 6-4 on the year with a home win over the Washington Wizards, with Nickeil Alexander-Walker dropping 28 points, leading three Hawks starters in double digits as they came away winners in a high-scoring 139-132 contest. For the Wizards, it was Kyshawn George that dominated, posting 33 points in the loss, with Trae Young tallying 23-10 in the absence of Anthony Davis.
With a win, the Minnesota Timberwolves, without Anthony Edwards have now moved to 7-3 on the season behind 23 from Jaden McDaniels and 28 from Ayo Dosunmu, as the stars of the team have stepped up without their most important player. In the loss, Jeremiah Fears posted 24-5-5 for the New Orleans Pelicans, but it wasn't enough as they fell 115-109 at home, falling to 4-5 on the new campaign.