After seven seasons with the Lakers, he was traded to the Philadelphia 76ers in 2012 as part of a four-team deal that sent All-Star center Dwight Howard to Los Angeles.

He signed as a free agent with the Cleveland Cavaliers, where he briefly played before being traded to the Chicago Bulls, who subsequently released him.

For most of his freshman year, he attended West Windsor-Plainsboro High School North located in Plainsboro, New Jersey.

In a game against the Miami Heat on January 16, 2006, Bynum matched up against former Laker center Shaquille O'Neal for the first time.

In March, there were reports that he could return before the end of the 2007–08 season or the first round of the playoffs;[30][31] however, Lakers coach Phil Jackson said that he did not foresee Bynum making serious contributions any time soon in April.

[33] He missed 46 games due to the injury,[34] and finished the season with averages of 13.1 points, 10.2 rebounds, and 2.1 blocks and a .636 field goal percentage.

In September 2008, Bynum said that he was 100% healthy and was ready to participate in training camp, which was scheduled to begin at the end of the month, after working with his trainer.

[36] Bynum set a new career high in scoring with 42 points to go along with 15 rebounds (8 offensive) and 3 blocked shots on January 21, 2009, against the Los Angeles Clippers.

[49] A longer than expected recovery period was needed for Bynum's surgery that caused him to miss the beginning of the 2010–11 NBA season.

He acknowledged that his doctor told him in advance that he might need more repair to the knee based on findings once the surgery began.

Bynum said he would make the same decision again to delay the surgery until after his vacation, even with the knowledge that it would cost him a portion of the upcoming regular season.

[50] Kevin Ding of the Orange County Register and Michael Rosenberg of Sports Illustrated criticized Bynum for his summer activities and not expecting complications based on his history with injuries and recovery time.

[58] On March 20, Bynum was suspended for two games by the NBA for a flagrant foul on Michael Beasley of the Minnesota Timberwolves.

[66] In his first game of the season after serving his suspension, Bynum scored 29 points on 13 for 18 shooting and grabbed 13 rebounds, leading the Lakers to a 92–89 victory over the Denver Nuggets.

He led the Lakers to a 3–1 week, leading the West in rebounding (14.8 rpg) and placed second in scoring (27.5) while shooting .665 from the field (fourth in the Conference).

[70] On March 28 against the Golden State Warriors, Bynum was benched by coach Mike Brown for the remainder of the third quarter after attempting an ill-advised three-point field goal with 10:05 left and the Lakers leading 56–50.

Bynum did not join his teammates in huddles during multiple timeouts in the fourth quarter, instead sitting by himself toward the end of the bench.

Bynum ended the season tied with Oklahoma City All-Star guard Russell Westbrook at 10th overall in Player Efficiency Rating (PER) with a PER of 23.00.

[74][87] On August 10, he was traded to the Philadelphia 76ers in a four-team deal that also sent Dwight Howard from the Magic to the Lakers and Andre Iguodala from the 76ers to the Denver Nuggets.

[88] The Magic decided against receiving Bynum due to concerns over his knees and his upcoming free agent status.

[89][90] About a week before training camp, Bynum underwent Orthokine treatments on both of his knees to stimulate healing for his arthritis.

As a precaution at the start of camp, the 76ers decided to hold Bynum out from basketball activities for three weeks after he experienced discomfort in his knees.

[91][92] He did not practice or play with the team prior to the season, and suffered another setback after injuring his left knee while bowling.

[94] Since training camp, Bynum had been firm that he would make his debut for Philadelphia, and had targeted the All-Star break for his return.

[95] On March 19, Bynum had season-ending arthroscopic surgery on both knees, ending his 76ers tenure without appearing in a game for the franchise.

On December 28, Bynum was suspended indefinitely by the Cavaliers for conduct detrimental to the team;[103] he had been thrown out of practice after shooting the ball every time he received it, regardless of how far he was from the basket.

[105] The same day, he was waived by the Bulls in a salary cap move that was projected to save Chicago more than $20 million and provide relief from paying the NBA's luxury tax.

[108][109] Coach Frank Vogel planned to give Bynum one to two weeks of practice before evaluating if he was ready to play.

[111] He appeared in only two games before Indiana declared him out indefinitely with swelling and soreness in his right knee;[112] he missed the remainder of the regular season.

[113] On May 7, before game 2 of the second round of the 2014 NBA playoffs against Washington, the Pacers announced that Bynum would miss the remainder of the season and would no longer be involved in team activities.