Charlotte dominated ECU in rebounds, 45-21, and points in the paint, 46-24, which were both strengths of the Pirates in their first five games.
"We didn't have a team effort rebounding," said senior forward Maurice Kemp. "In all spots, we didn't do what needed to do."
Kemp led all ECU scorers for the fifth time this season with 16 points, but it was a pair of 49ers who stole the show.
Before 7,896 raucous fans inside Dale F. Halton Arena, senior forward Chris Braswell had a game-high 18 points while freshman forward Willie Clayton finished with 14 points and a game-high 13 rebounds.
One of lingering concerns for the Pirates remains three-point shooting. After six games, the team has only shot 26 percent from beyond the arc.
"We've had some that we have to be able to hit," said ECU head coach Jeff Lebo. He went on to say that they couldn't shoot anything "consistent from the perimeter."
The physicality the 49ers brought to the table created problems for Lebo and got key players into foul trouble early on. At halftime, point guard Miguel Paul and forwards Marshall Guilmette and Robert Sampson each had three fouls.
With ECU's lack of discipline, Charlotte began the game on a 28-10 run. The closest the Pirates ever got after that was 37-28 with 19:50 left to play, but the 49ers always had an answer.
Charlotte now leads the all-time series against ECU 15-6. The 49ers won last year's meeting in Greenville by the same exact score.
Charlotte native, Paris Roberts-Campbell scored all of his 12 points in the second half while former Charlotte shooting-guard and current Pirate, Shamarr Bowden was held scoreless in his return.
ECU will return home to host Division II Saint Andrews Tuesday, before facing North Carolina on Dec. 15 in Chapel Hill.