Delle Donne scored 10 points during a decisive 21-8 Delaware (23-3, 14-0) run to close the half, giving the Blue Hens a 41-24 lead.
Delle Donne jumped up two spots on the NCAA all-time career points list, finishing the night in 20th place with 2,758.
Delaware has now won 34 straight Colonial Athletic Association games and has beaten George Mason four straight times.
Amber Easter led George Mason (8-16, 3-10) with 14 points.
The Patriots never pulled closer than 10 points in the second half despite Delaware going 6:46 without a made field goal at one point. Delaware outshot George Mason 44.4 percent (24 for 54) to 33.9 percent (21 for 62).
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