Taj Gibson had 15 points and eight rebounds for Chicago (5-3), which won its fourth straight game behind 11-of-19 shooting from 3-point range.
"We got off to a good start," Bulls coach Tom Thibodeau said. "(The Pacers) missed some shots that they usually make. Overall, I thought it was a good win. We played very unselfishly."
Indiana (9-1) was the NBA's first 9-0 team since the 2002-03 Dallas Mavericks, who started 14-0. The nine wins to start a season matched a franchise record.
Nursing a sore right hamstring, Rose was effective in his 30 minutes on the court. He weaved around and penetrated the league's best defense, which hadn't allowed more than 91 points to any opponent this year.
No Running With The Bulls
The Pacers defense had thrived in the team's first nine games of the season, all wins. But in Saturday night's loss to the Bulls, the unit couldn't keep up with Derrick Rose and Co. Here's a look:
Opp FG pct
Opp 3-pt FG pct
-- ESPN Stats & Information
Rose was injured Monday against Cleveland, and did not play in Chicago's 96-80 win Friday at Toronto.
"I was just being smart about the situation," he said about not playing Friday. "This is my first time having a hamstring injury. I don't know how it would go if I had played last night. I don't think I'd be able to play tonight."
The 25-year-old former MVP shook off the rust after a pair of early off-balance misses. He sank a floater in the lane 3 minutes in, followed by a 3-pointer 30 seconds later to ignite a 12-2 first-quarter run for Chicago.
"They were giving me shots," Rose said. "I've got to take those shots. I saw some go in, so I kept shooting."
Rose cozied up at the 3-point arc in the second quarter, knocking down all three attempts as the Bulls took a 25-point advantage into the half. He finished 6 for 11 from beyond the arc.
"Most of Rose's 3s were pretty well contested considering his speed," Pacers coach Frank Vogel said. "You can't just jam him. You have to give up something. You have to give them credit."
Kirk Hinrich came off the bench to contribute 13 points, eight assists and four rebounds for the Bulls, who avenged a 97-80 loss at Indiana on Nov. 6.
The Pacers lost despite having all five starters -- and two reserves -- score in double-digits.
SN: Pacers lose to Bulls
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Roy Hibbert led Indiana with 14 points a day after posting season-highs with 24 points and eight blocks.
Chicago held Paul George to 12 points. He entered the game seventh in the NBA with 24.6 points per game. George and Lance Stephenson combined to miss all seven of their 3-point attempts, and the team made just 25 percent.
"I understand I'm going to have nights like this when shots aren't falling," George said. "I just don't want to have many."
The Pacers were coming off their most lopsided win of the season, a 104-77 drubbing of Milwaukee.
Chicago reached triple-digits for the second time this season. ... Deng led Chicago in scoring for the fourth time this year. ... Pacers forward Danny Granger (strained left calf) was inactive Saturday. He has yet to play in a game this season.