The Lakers scored the first 12 points of the fourth quarter with Bryant resting and went on to a 134-114 win.
Bryant scored 32 points and Jordan Farmar had a career-high 18 points for short-handed Los Angeles, which has won four straight. Andrew Bynum added 17 points and 10 rebounds in his first start as the Lakers rolled to the highest point total in the league this year.
Bryant, normally the catalyst during such runs of Lakers dominance, liked what he saw in the fourth.
"It feels great," he said. "Everybody's contributing. When we have games like tonight, particularly when we're on the road, that's when everybody gains confidence and really starts finding their groove."
"We lost two guys that are a part of our brotherhood," said Bryant, who has been surrounded by trade rumors himself this year. "That's always tough. I don't think anybody here feels particularly good about it. That's life.
"Everybody can feel down about it, but you can mope and moan about it on the bus. We came out here and took care of business."
Shawne Williams led the Pacers (4-7) with a career-high 24 points, and Jamaal Tinsley added 10 points and 10 assists. It was Indiana's worst home defeat since a 24-point loss to New Jersey on March 4, 2001.
The Lakers (7-3) have won their past three games by a combined 60 points. Eight Lakers scored in double figures for first time since Nov. 26, 2003.
"Everybody's playing a lot of minutes," Lakers coach Phil Jackson said. "Some of it's ball movement, some of it's players shooting in their range."
Los Angeles shot 61 percent to lead 71-63 at halftime. Bryant scored his average, 26 points, before the break. He made five of seven 3-pointers in the first half, often leaving his arm in the air well after his follow-through. Bynum had three powerful dunks before halftime.
Danny Granger tried to get the Pacers back in the game. He cut the Lakers' lead to 87-74 with a layup in the third quarter. He then blocked Bryant's shot against the glass at the other end, and converted another layup to get Indiana within 11.
The Lakers quickly recovered and led 104-90 heading into the fourth quarter.
Los Angeles pulled away by holding the Pacers to 30 percent shooting in the final period. The bench scored 25 of the Lakers' 30 points in the quarter.
"We got pounded by a very, very good basketball team that seemed quicker at every position," Pacers coach Jim O'Brien said. "We didn't have the energy necessary to give them any kind of a game."
The Lakers shot 58 percent and made 13 of 25 3-pointers.
"We moved the ball extremely well and we were shooting the ball like we were practicing," Bryant said.
Bynum got the best of his matchup with Indiana forward Jermaine O'Neal. He made all six of his shots and had four blocks. In one sequence in the fourth quarter, he blocked back-to-back attempts by O'Neal.
O'Neal went 4-for-13 from the field to finish with 14 points and three rebounds.
Bynum said he wanted to make the most of his opportunity with Cook out of the lineup.
"I just think it was a case of me playing more minutes than usual, and I think if my minutes go up, my production should go up."
Lakers C Kwame Brown was out with a sprained knee and ankle. ... The Lakers shot 67 percent in the first quarter, yet only led 37-35 at the end of the period. ... Los Angeles G Coby Karl played for just the second time this season and scored the first points of his career on a pair of free throws with 26.1 seconds left. He had played one minute in the season opener against Houston. He played three minutes against the Pacers. ... The Lakers had lost three in a row at Conseco Fieldhouse. ... Indiana's 103 field-goal attempts were a Conseco Fieldhouse record.