Junior Rebecca Collimore set up senior co-captain Lauren Johnson at 13:16 before scoring a goal of her own 42 seconds later and it was all Shenandoah (5-3, 1-0 ODAC) in the league opener for both schools.
Guilford (3-4, 0-1) avoided the shutout with a goal nine seconds prior to the end of the first half. The Quakers scored their second goal on an unassisted tally in the 69th minute.
Sophomore Emily Yergin, who finished with two goals, answered that initial GC tally with her second goal of the game 87 seconds into the second half.
Following that opening pair of goals, SU scored its first half tallies in the 22nd (Yergin), 36th (Sara Fuller), 42nd (Liz Keefer) and 43rd (Keefer) minutes. Yergin's goal, an unassisted tally, stood up as the game-winner. She has three game-winning goals this season.
Collimore, Fuller and Teresa Zielinski all had assists during this run.
Keefer finished off her hat trick as Collimore dished out her third assist of the game at 74:32.
The Hornets dominated possession throughout the game, taking 27 of the game's 31 shots and earning 12 of the 13 corners.
Guilford starting goalkeeper Becca Banks had seven stops in 45 minutes of action.
Shenandoah continues this homestand on Tuesday with a 7 p.m. non-league contest versus Mary Washington.