Justin Sears added 16 points and Makai Mason 14 for the Bulldogs (12-5, 3-0 Ivy), who won their seventh straight.
Yale shot better from the field (30 for 50) than it did from the foul line (17 of 33). Nick Victor had nine rebounds to go with six points as the Bulldogs had a 41-25 rebounding advantage.
Matt Howard made 7 of 10 shots and led Penn (6-10, 0-2) with 17 points but the Quakers shot 40 percent (20 of 50) and were just 13 of 23 from the line.
Yale scored the first eight points but never got the lead past 10. Sears' layup made it 41-31 at the half. The Bulldogs steadily pulled way in the second half.