Carlos Boozer had 17 points and Luol Deng 14 for the Bulls, who outscored the Hornets 25-14 in the fourth quarter to close out a five-game road trip at 3-2.
One game after outdoing Utah's Derron Williams in Chicago's win over the Jazz on Wednesday night, Rose got the better of the Hornets' Chris Paul, who had 15 points.
Marcus Thornton had a season-high 24 points and David West added 17 for the New Orleans, which missed 13 of 39 free throws in losing for the seventh time in nine games.
The Bulls took the lead for good when C.J. Watson's transition 3, set up by Ronnie Brewer's block of Thornton's fast-break layup attempt on the other end, ignited a 9-0 run.
Watson also turned a steal into a fast-break layup during the surge, which put Chicago ahead 89-80 with 5 minutes to go. New Orleans responded with two quick baskets, but Rose set up Boozer's inside basket with a bounce pass into the paint, then made a difficult, off-balance baseline jumper to make it 93-84 with 2:27 left.
The Hornets could not recover after that.
Keith Bogans had 11 points for Chicago, which shot 51.5 percent (35 of 68) and outscored New Orleans 36-20 inside. Kurt Thomas grabbed 11 rebounds for the Bulls, who outrebounded New Orleans 47-26. Chicago also made 21 of 22 free throws.
New Orleans, which shot only 40.6 (28 of 69) for the game, led by 12 when Paul baited Rose into a shooting foul behind the 3-point arc and made all three free throws to put the Hornets up 61-49 early in third quarter. Shortly after, however, Thomas' short baseline jumper started a 12-1 run highlighted by Bogans' third 3 of the game and another by Rose that made it 64-63.
Thornton checked back in and immediately hit a 3, and the Hornets began to control the pace again. They were unable to pull away, however, because they missed eight free throws in the third quarter alone and led only 74-72 heading into the final period.
Chicago finally pulled back into a 76-all tie when Rose intercepted David Andersen's pass and finished a fast break with a full-speed, spinning dribble past Thornton for a layup.
Chicago and New Orleans entered second and third in the league in scoring defense and both teams spent most of the opening quarter shooting worse that 40 percent. The Hornets shot only 33 percent (7 of 21) in the opening period, but did not turn the ball over in the period, and Chicago's lead was only 24-22 when the quarter ended.
Thornton changed the complexion of the game in the second quarter, when he scored 14 of his points. He drained back-to-back 3s on the heels of a long-range shot by Paul during an 11-0 run that West capped with a tough turnaround, putting New Orleans ahead 53-42 at halftime.
Notes: Chicago's only missed free throw came on an airball by Brewer late in the third quarter. ... Chicago C Joakim Noah missed his 28th game as he recovers from surgery to repair a tendon in his right hand. ... New Orleans fell to 6-2 against the top five teams in the Eastern Conference and to 11-2 at home against the East. ... Announced attendance was an overflow crowd of 17,831, the Hornets' sixth sellout this season. ... The Hornets had only two offensive rebounds, tying a franchise all-time low.