Charlotte scored six times in the third to break a 1-1 tie and beat the Bulls 11-1 on Friday.
Durham, now 0-2 on a six-game road trip, has lost three meetings with Charlotte at Knights Stadium by a combined score of 35-10.
The Bulls scored first on this night, with the run coming on a botched rundown in the opening inning.
However, Durham, which had the first three runners reach in the frame, hit into double plays in the first four innings against lefty Arnie Munoz (7-10).
Meanwhile, John Webb (8-5), who had allowed only two runs in his previous two starts, gave up a two-out homer to Joe Borchard in the second to tie the score.
Webb then allowed a grand slam to Roosvelt Brown and a two-run homer to Borchard in the third and left trailing 7-1.
Charlotte has now outhomered the league's top home-run hitting team 7-0 over the last two nights.
Durham had a chance to cut into the lead in the fifth, but left the bases loaded, and Charlotte capped the scoring with a four-run eighth.
Trenidad Hubbard had a perfect night at the plate, going 2-for-2 with two walks, and Rob Bell gave Durham three scoreless innings in relief.
The Bulls face Charlotte on Saturday at 7:15 with lefty Chris Seddon on the mound. Coverage on WDNC 620 AM begins at 7 p.m.
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