West scored six of his team-high 17 points down the stretch as the Cavaliers, trailing 91-80 with 4:14 left, finished the game on a 20-2 run. Daniel Gibson made the go-ahead basket with 1:22 left.
"It was a good win," West said. "I think it will be good for the confidence of our team."
West was away from the team Oct. 4-15 and made his first preseason appearance Thursday against San Antonio. He said Friday he had been dealing with depression and a mood disorder.
"It was only the second time I played at game speed," he said after playing 28 minutes. "I don't have a problem with conditioning. It's more getting in the game rhythm and getting the shots."
West hit a jumper and a 3-pointer to help Cleveland's rally. Sasha Pavlovic's 3-pointer cut the lead to 93-92 with 1:53 to go. Gibson scored on the Cavaliers' next possession.
After a turnover, Anderson Varejao's basket in the lane gave Cleveland a 96-93 lead with 46 seconds left. The 76ers missed a 3-pointer, which led to a fast-break basket by J.J. Hickson with 29 seconds left. West's two free throws capped the comeback.
"Their group towards the end played very well while we relaxed," Philadelphia coach Maurice Cheeks said. "That, obviously, was the difference in the game."
Cleveland is 1-4 while Philadelphia fell to 3-2.
Andre Iguodala scored 17 points for Philadelphia and Donyell Marshall added 15 on 5-of-6 3-pointers. Lou Williams also scored 15.
LeBron James scored 16 points in 26 minutes.
"The bench did a great job and made some big plays down the stretch," he said.
The game was played with an intensity usually reserved for the regular season. Cleveland's Mo Williams and Philadelphia's Andre Miller were assessed double technicals midway through the first quarter. Williams was given a second technical and ejected by referee Sean Corbin 19 seconds later.
"I said something," Williams said. "It was more directed toward myself. It wasn't the right choice of words at the time. I understand his decision for the ejection."
Cleveland center Zydrunas Ilgauskas, who had 17 points, was given a technical in the third quarter. West was assessed a flagrant foul in the second quarter and players from both sides dove to the floor several times to grab loose balls.
Williams' ejection brought a quick end to coach Mike Brown's plan to play his starting five into the second half. Williams, a key offseason acquisition from Milwaukee, is expected to provide vital help for James.
James played 17 minutes in the first half and nine in the third quarter. Brown had Ilgauskas, Ben Wallace and Pavlovic, who all started, on the floor in the fourth quarter.
Philadelphia played without forward Elton Brand, whose wife gave birth to a baby Thursday, and center Samuel Dalembert (sprained right knee).
Cavaliers rookie forward Darnell Jackson, who helped Kansas to the national title last season, is out indefinitely with a fractured left wrist.