The Hornets had trailed the entire game until mounting a furious fourth-quarter rally, during which they erased a 12-point deficit and tied it up 92-92 on an Austin Rivers trey with 50 seconds remaining.
But New Orleans' Greivis Vasquez missed a layup with 11 ticks left and Lillard then connected from long range, icing the contest for Portland, which improved to 3-1 on a six-game home stand.
Lillard finished with 16 points and J.J. Hickson added 24 with 16 rebounds for Portland.
LaMarcus Aldridge supplied 20 points for the Blazers before leaving late in the game with an apparent ankle injury.
Ryan Anderson put in 26 points and Vazquez finished with 23, eight rebounds and 11 assists for the Hornets.