The Hornets lost their seventh game in a row and needed a three-pointer from Marco Belinelli with 0.5 seconds left to avoid a franchise-low in points scored.
"We couldn't throw it in the ocean," said New Orleans coach Monty Williams.
Indeed, the game started and ended as a laugher: Actor and comedian Will Ferrell, in town shooting a movie, handled the intros for both teams before the game.
Rose, who left Monday's win over New Jersey with lower back spasms, played only 22 minutes and sat the entire fourth quarter. He had six points, six assists and five rebounds.
"He says he feels pretty good," Bulls coach Tom Thibodeau said of the reigning MVP.
Chris Kaman had 17 points and nine rebounds off the bench to lead the Hornets and Belinelli scored 13. New Orleans fell to 4-22.
The Bulls moved to 22-6 on the season and 5-2 on a nine-game road trip that ends with visits to Charlotte and Boston. They won their fourth straight game and third in a row by 20-plus points.
The best team in the Eastern Conference had no trouble with the worst team in the Western Conference, leading by as many as 28 points in the wire-to-wire win.
"The way the ball's moving, it's not sticking anywhere," said Thibodeau. "We're getting good shots."
The Bulls shot 52.4 percent and led 23-14 after the first quarter. In the second, they went up 15 on Taj Gibson's fastbreak dunk and took a 42-27 lead on Kyle Korver's three-pointer from the left side in transition.
It was 44-31 at halftime and 70-46 going into the fourth quarter. The Bulls went ahead by a game-high 28 points on John Lucas' three-pointer in the final minutes.
The Bulls have won seven in a row over New Orleans and 10 of the last 12 meetings...Among Ferrell's introductions was this one: "At guard, No. 1, his favorite movie is 'The Notebook' ... Derrick Rose!"