The victory was the first over the Colonels since a 69-62 victory on January 4, 1983 and the first meeting between the schools in 25 years.
The Norse took a 37-29 advantage at intermission, opened the second half with a 10-1 run and maintained a double-digit advantage the rest of the way.
McDonald hit 10 of 13 from the field to score 23 points and grabbed nine rebounds in leading the Norse (7-3). Williams was9-of-10 shooting and had a career-best five steals. Northern Kentucky shot 60 percent from the field (39 of 65), despite 5-of-22 shooting from 3-point range.
Jackson Davis had 13 points off the bench to lead Eastern Kentucky (4-6), which shot 45.5 percent from the field (25 of 55) and hit 8 of 19 from beyond the arc.