Amber Harris had 27 points and 12 rebounds and No. 7 Xavier overcame a slow start to beat Charlotte 82-61 on Saturday night.
Ta'Shia Phillips added 22 points and 13 rebounds while Tyeasha Moss had 13 points for the Musketeers (16-2, 5-0 Atlantic-10), who won their sixth consecutive game.
Shannon McCallum scored 23 points and Epiphany Woodson added 13 for Charlotte (15-5, 3-2), which saw its three-game winning streak end.
Xavier, which has been ranked in the Top 25 for 61 consecutive weeks and rose as high as No. 4 earlier this season, shot 50 percent from the field.
Charlotte entered as the conference leader in rebounding differential at 11.2 per game, but Harris and Phillips led the Musketeers to a 45-30 edge Saturday.
However, it was Charlotte that had the hot hand early in the first half, scoring seven of the game's first nine points and pulling ahead 12-8 on McCallum's jumper with 14:23 left.
But the 49ers cooled off after that, going more than 7½ minutes without a field goal. That allowed the Musketeers to break loose, with Phillips' layup with 8:04 left in the half putting Xavier up 21-12.
Charlotte managed to pull within five points three times in the closing minutes — the last at 27-22 on McCallum's tip in with 2:08 left — but Harris followed that with a 3-pointer and layup to push the Musketeers' lead to 32-22, its biggest of the half.
They led 32-25 at the half.
The 49ers put on another surge in the opening minutes of the second half, cutting Xavier's lead to 37-35 on Paige McCallum's 3-pointer with 16:35 left, and pulling within 47-43 on Shannon McCallum's jumper with 12:24 remaining.
The Musketeers responded with a 14-1 run, with Special Jennings' layup with 8:35 left giving Xavier a 63-44 lead.
Charlotte would put together one final run, scoring 10 unanswered points capped by Woodson's 3-pointer with 6:01 left to pull within 63-54. That's as close as the 49ers could get as the Musketeers scored 19 of the game's final 26 points over the final 5:49.