New York trailed 63-40 at the half and never got closer than 91-82 with 3:44 left in the fourth.
LeBron James led the victory with 33 points, eight rebounds, nine assists and three steals.
Mo Williams and Daniel Gibson also hit double digits in scoring, while Zydrunas Ilgauskas and Anderson Varejao had were in double figures for rebounds for the Cavaliers, who have won four of seven to start the new NBA season.
David Lee's 21 points with six rebounds led New York.
Larry Hughes added 18 points, while Danilo Gallinari had 17, Al Harrington 14 and Wilson Chandler 11 for the Knicks, who have lost their last six games against Cleveland and 10 of 13.