Bucknell earned a trip to college basketball's big show for the second straight year and for the sixth time overall. The Bison will be seeking their first NCAA victory since an upset decision over Arkansas seven years ago.
Lafayette closed within 43-40 with 6:34 to go on a jumper by Dan Trist, but then went scoreless for the next 3:30.
Bucknell produced 12 straight points, touched off by a hook shot from Muscala.
Muscala finished with 20 points and 11 rebounds, helping the Bison improve to 28-5. Bucknell won the regular-season championship in the Patriot League and hosted the title game against the second-seeded Leopards.
Joe Willman added 14 points for Bucknell, which converted 18 free throws to seven for Lafayette.
Joey Ptasinski had 15 points off the bench to lead the Leopards (19-15).