Knight connected on four 3-pointers and Josh Harrellson contributed 12 points and 11 rebounds as Kentucky (12-2) outscored the Quakers 53-30 in the second half after ending the first 20 minutes with only a one-point lead.
Darius Miller chipped in with 11 points, seven rebounds and six assists in the Wildcats' seventh straight victory.
Penn (5-6) got 22 points from Tyler Bernardini and 16 from Miles Cartwright.
Former Titans kicker dies in car crash
UPI Sports Results for September 20, 2014