Walker also drew contact along the way, making 9 of 10 free throws, an area where the Pacers struggled all game. Indiana shot just 59 percent from the free throw line.
Gerald Henderson added 18 points for the Bobcats and Ramon Sessions chipped in 11 points, including a big 3-pointer early in the fourth quarter.
Tyler Hansbrough and Lance Stephenson led the Pacers with 15 points each.
The Bobcats were the worst shooting team in the league last season, but they came out strong building a 12-3 lead. That was short-lived as they quickly cooled off going more than 6 minutes without a point. The Pacers grabbed the lead behind 12 hard-fought points by Hansbrough and took a 43-39 halftime lead.
Walker scored eight quick points to start the second half, giving the Bobcats a lead they would never relinquish.
Indiana played without forward Danny Granger, the team's leading scorer the past five seasons, who continues to be sidelined indefinitely with soreness in his left knee. Before the game, coach Frank Vogel said they are still awaiting the medical results of a second opinion on his knee.
The Pacers shot just 36.5 percent from the field.
"It was a tough shooting night but you have to give the Bobcats credit," Vogel said. "Kemba Walker was sensational. We turned the ball over too much and we couldn't knock down our free throws."
Michael Kidd-Gilchrist, the No. 2 overall pick in this year's draft, struggled offensively for the Bobcats going 1 for 7 from the field and he didn't play much down the stretch.
However, he played hard with seven rebounds and was impressive at times on defense.
In the second quarter Kidd-Gilchrist skied to block a shot by 7-foot Roy Hibbert in the lane, igniting a fastbreak layup and three-point play on the other end by Walker.
"I was nervous coming into this game," Kidd-Gilchrist said. "I'm a rookie. So, I was just nervous. But I thought I did pretty well."
NOTES: Pacers F Sam Young only played 20 seconds before leaving with a right shoulder injury. He was hurt when he got Henderson in the air with a pump fake and Henderson's leg landed on his shoulder on the way down. ... Former professional wrestler Ric "The Nature Boy" Flair attended the game. ... The Bobcats won their season opener last year before the season quickly began to unfold.