Both teams had lost two in a row coming into the game and Portland took advantage of the absence of New York's Carmelo Anthony to pull away late.
Anthony has been nursing a sore knee, which he reinjured in a loss to Denver on Wednesday.
Lillard hit 11-of-18 shots off the bench and scored 26 points while the Trail Blazers were shooting 51 percent. LaMarcus Aldridge added 22 points and Nicolas Batum had 18.
Portland overcame an eight-point deficit after one period to take a 14-point cushion into the fourth quarter. New York rallied to within six midway through the final period but came no closer.
J.R. Smith led the Knicks with 33 points, but they saw their lead over Brooklyn in the Atlantic Division cut to a single game.