Elena Delle Donne scored 28 points and pulled 53, on Thursday.
Danielle Parker added 14 points and 12 boards, while Lauren Carra contributed 11 points for Delaware (25-1, 16-0 CAA), which won its 15th straight game after the Blue Hens' lone loss of the season.
Taleia Moton paced George Mason (13-14, 7-9) with 18 points and Joyous Tharrington netted 10 for the Patriots, who shot 32.4 percent in the game, including an 0-for-10 mark from three-point range, en route to losing for the third time in four tries.
Delaware controlled the game from the beginning, opening the contest with a 15-4 run to take a lead the Blue Hens never lost.
Moton's jumper brought George Mason back within single digits, but a pair of Parker foul shots put Delaware back up by 11 and the Hens held a double-digit advantage for the remainder of the game.
A 10-2 spurt near the end of the first half gave Delaware its largest lead so far in the game, 38-19, before Talisha Watts' free throws in the closing seconds made the score, 38-21, at the half.
The Patriots never threatened in the second half, trailing by at least 11 points and by as many as 19 in the final 20 minutes.