Lewis also had five assists and seven steals as Canisius forced 19 turnovers and had 15 assists on 24 field goals.
Jamal Reynolds added 10 points for Canisius (6-4). The Griffins made 24 of 55 field goals, including 8 of 18 from 3-point range.
Cullen Hamilton led Holy Cross (5-4) with 10 points.
Canisius scored the final five points of the first half for a 24-18 lead at the break.
Taylor Abt made 1 of 2 free throws to bring Holy Cross within 33-31 but Canisius went on an 11-0 run, led by Lewis' five points, for a 44-31 lead. After another Holy Cross 1-for-2 trip to the line, Canisius scored the next six points for an 18-point advantage and the lead would grow to as large as 25.