Jefferson had 23 points and 12 rebounds, both highs for the year. The Bobcats outscored the Bucks in every quarter in what was Milwaukee's 11th straight loss.
The Bucks have just two wins this season, fewest in the Eastern Conference.
Gerald Henderson added 19 points and six rebounds for Charlotte, which had lost its previous two games.
Charlotte owned a 54-38 edge in rebounding to make up for its 17 turnovers.
Brandon Knight scored 17 points to lead the Bucks.