Harvard scored twice in a 24-second span in the third quarter to take a 27-18 lead.
The Crimson pulled ahead 20-18 on Conner Hempel's 5-yard pass to Anthony Firkser with 4:43 to go. On the first play after the kickoff, Matt Koran returned Holy Cross quarterback Peter Pujals' fumble to the 18. Casten followed with a touchdown run on the next snap.
Casten scored on a 3-yard run 5 seconds into the fourth to make it 34-18. He also opened the scoring in the first quarter with a 3-yard run.
Hempel was 11 of 13 for 137 yards and two touchdowns, and Scott Hosch was 8 of 12 for 90 yards.
Pujals was 26 of 41 for 233 yards for Holy Cross (2-2). Jake Wieczorek had 11 catches for 98 yards.
Harvard won a share of its 15th Ivy League title last season.