Elton Brand led the 76ers with 24 points, Andre Iguodala added 16 and Andre Miller had 12 points and 12 assists.
After struggling in his first preseason game, Brand was dominant in the first quarter, scoring 18 points on 7-for-8 shooting to give Philadelphia a 38-22 lead at the end of the quarter.
The Knicks opened the second quarter with a 23-6 run to take the lead with 4:41 remaining and built a 60-51 edge at halftime. New York extended its lead to 87-77 after three quarters and built an 18-point lead in the fourth.
Sixers starting forward Thaddeus Young left the game late in the third quarter with a left-eye corneal abrasion and Lou Williams left in the fourth with a lacerated chin that required three stitches. Neither returned.
New York played without several key players, including first-round pick Danilo Gallinari (lower back), Allan Houston (quadriceps) and Eddy Curry (coach's decision).