Holiday, who was 3 for 9 from the field after three quarters, drained three 3-pointers and five of six shots the rest of the way. The 76ers trailed 73-67 at the end of the third, but Holiday scored 10 points down the stretch as Philadelphia extended an 84-83 lead to 98-89.
Evan Turner added 21 points and Spencer Hawes scored 17 for the 76ers, who won for the third time during a franchise-record five-game road trip to start the season.
Eric Gordon led New Orleans with 22 points after missing four consecutive games with a bruised knee. Carl Landry added 21 points and eight rebounds while Jarrett Jack had 19 points and 11 assists, but it wasn't enough to keep the Hornets from losing their fourth in a row.
Philadelphia, which trailed 73-65 late in the third quarter, went on a 9-0 run to take the lead early in the fourth, scoring on four consecutive trips down the court. Elton Brand's dunk closed the gap to 73-67 entering the fourth. Holiday followed with a 3-pointer, Brand then hit a face-up shot and Turner scored as the 76ers went ahead.
The lead changed hands six times in the next 6 minutes, with neither team going ahead by more than three points until Holiday hit another 3 to give the 76ers an 89-83 advantage.
The Hornets cut the deficit to 89-87 on a pair of free throws by Jack and a floater by Jack after Gordon's steal, but Holiday responded with another 3-pointer at the 2:40 mark.
New Orleans center Emeka Okafor missed two free throws, and Holiday hit a leaner to give Philadelphia a 94-87 lead.
After Landry scored inside, the 76ers' Andre Iguodala soared to the rim for an emphatic dunk to make the score 96-89. It was only his second basket in 10 shots.
Holiday sealed the victory with a shot just inside the 3-point line with 36.6 seconds left as Philadelphia took its largest lead to that point, 98-89.
The 76ers, who had zero points off turnovers through three quarters, scored 13 off six Hornets miscues in the fourth. Philadelphia also scored three baskets on putbacks in the quarter against the NBA's leading rebounding team.
Those factors made up for a lack of outside shooting from anyone other than Holiday. Iguodala and Louis Williams, who had combined to go 21 of 36 on 3-pointers through four games, combined to miss all five of their long-range attempts, with Iguodala misfiring on four.
The Hornets led for almost the entire first three quarters. Gordon scored seven of their first nine points and hit his first four shots.
Showing no signs of the knee injury that kept him out for four games, Gordon drove the baseline for an easy basket, followed with a layup in transition, drained a 3-pointer off an offensive rebound, knocked down an outside shot and hit a midrange jumper, all in the first 9:30.
He cooled off the rest of the way, finishing 8 of 22 from the floor. It was Holiday's turn to heat up in the fourth quarter.
Notes: The Hornets and 76ers were part of a three-team trade announced earlier Wednesday, but it had no impact on the game. The Hornets received forward Xavier Henry from Memphis, and Philadelphia sent Marreese Speights to the Grizzlies in return for second-round picks from New Orleans and Memphis. Henry, out with an ankle injury, said he hopes to play within two weeks. Speights did not get off the bench in the 76ers' first four games. ... The last time Philadelphia played in New Orleans, it was at the end of a season-long, eight-game road trip in 2010-11.