Cameron Ayers opened the second half with a 3-pointer to make it 30-20 and the Bison (16-3, 3-0) maintained a double-digit advantage the rest of the way to win their third straight game and fifth in the last six.
The win ties the second-best start in program history after 19 games. Bucknell was 17-2 in 1983-84 and also 16-3 in 2005-06.
Muscala was 12 of 24 from the field as the Bison shot 44.6 percent (29 of 65). Ayers added 12 points and Joe Willman 10.
The Leopards (8-12, 1-2) shot only 34.5 percent (19 of 55), making 1 of 13 3-pointers, to lose their ninth straight in the series.
Seth Hinrichs scored 12 points and Dan Trist added 11 for Lafayette.