The Bears were the first nationally ranked team to see action on the opening night of the 2012-13 college basketball season.
Baylor won a school-record 30 games last season and is favored to go deep into the NCAA Tournament this year.
Jefferson made 12-of-16 shots from the floor while Isaiah Austin added 22 points before leaving the contest early in the second half with a sprained ankle. Pierre Jackson pitched in with 14 points and 12 assists for the Bears.
Lehigh is also coming off a strong season, in which it became only the sixth 15th-seeded team to win a game in the NCAA Tournament. The Mountain Hawks stunned Duke in the opening round of last season's event.
CJ McCollum led Lehigh with 36 points and eight rebounds.
Lehigh stayed within 10 points through the first half, but Baylor built a 23-point cushion through the opening 9 minutes of the second period.