Alana Beard scored 17 points, Nikki Teasley had 15 and Nakia Sanford added 13 for the Mystics (3-10), who have won three of five after starting the season Oh-and-8.
Candice Dupree scored 26 for Chicago (6-7), which had won two of three.
Chasity Melvin had 14 points and 9 rebounds in the loss.
The Mystics led 46-36 at halftime.
They then opened the second quarter on a eleven-2 run.
Dominique Canty -- the Sky's second-leading scorer at 10-point-9 points per game -- hurt her ankle late in the first half and was helped off the floor at halftime.
She did not return to the game.