Gary Neal scored 15 points to help the Bobcats inch closer to a playoff berth.
The Bobcats (37-38) have the seventh-best record in the Eastern Conference. They entered 4½ games ahead of the ninth-place New York Knicks and needed four wins in the final eight games to clinch their first playoff berth since 2010. . One down, three to go.
The Bobcats raced to a 13-point lead in the first quarter, stretched it to 35 and never once let the Sixers threaten.
Michael Carter-Williams scored 22 points on 10-of-18 shooting for the Sixers. They have lost two straight since snapping an NBA-record tying 26-game losing streak on Saturday.
The Bobcats set the tone in the first quarter en route to putting away the lowly Sixers. Led by Jefferson, the Bobcats made 11 of their first 15 shots and finished with nine assists on 12 baskets.
Jefferson picked up where he left off in March, when he was named Eastern Conference player of the month. He averaged 24.7 points on 56 percent shooting (178-321), 10.6 rebounds and 2.2 assists. He was the first Bobcat to ever win the award.
He kept his hot hand rolling in the first game of April with a 13-point first quarter.
Jefferson finished 9 of 17 from the floor and made 7 of 10 free throws.
Even in a season that has them with the second-worst record in the NBA, this was as bad as the Sixers have played in weeks. Trailing by 13, the Sixers had five turnovers and only four baskets. They missed all seven 3-point attempts in the first half and finished 4 of 18 overall. The Sixers had two starters go scoreless in the half.
Charlotte, one of the few teams to lose to the Sixers this season, bust the game open with a 22-8 run in the second. Anthony Tolliver, who scored 16 points, hit a pair of 3s during the spurt and the Bobcats cruised from there.
The Bobcats continued doing the big things that have them within striking distance of Washington for sixth place. They had only nine turnovers (average a league-low 12.3), outrebounded the Sixers 47-32 and had three bench players score double digits.
NOTES: Charlotte F Josh McRoberts (left ankle) sat out. Cody Zeller scored nine points in his first career start. ... 76ers coach Brett Brown again said that injured rookie F Nerlens Noel likely will not play at all this season. "There's so much to weigh out if we're smart with this, and we will be," he said.