Zagunis' shot over the left field wall against reliever Gage Smith improved the sixth-seeded Hokies (37-19) to 2-0 in Pool B while dropping the second-seeded Seminoles (44-15) to 0-2 in Durham.
The Hokies took a 2-0 lead in the seventh on an RBI triple by Zagunis, who scored on Andrew Rash's sacrifice fly.
Stephen McGee's leadoff double in the ninth sparked a comeback for the Seminoles. Casey Smit's ground-rule double scored McGee from third. Pinch-hitter Josh Delph singled to right and pinch-runner Brett Knief beat the throw home.
Reliever Clark Labitan (2-5) earned the win. Smith (4-1) took the loss, allowing three hits, including Zagunis' blast.
The Hokies play seventh-seeded Georgia Tech on Friday. Florida State plays third-seeded Virginia on Saturday.