A narrator reveals that hidden within the SATs is a test designed to assess a student's capacity to fight, deceive, and kill. Those female candidates who excel in this covert evaluation are recruited into a clandestine paramilitary organization known as D.E.B.S., which stands for Discipline, Energy, Beauty, and Strength.
The focus of the story centers on one squad of D.E.B.S., led by team captain Amy, alongside the no-nonsense Max (played by Tammy Lynn Michaels), the French exchange student Dominique (portrayed by Shanti Lowry), and the rather uptight Janet (in the capable hands of Jill Ritchie). Together, they are tasked with battling the menacing and cunning villain, Lucy in the Sky (who is played by Clare Kramer).
In a clever spoof of prime-time television, there’s a recap segment titled "previous on D.E.B.S." where the team's superior, Mr. Tibbs, informs them that Lucy in the Sky has re-entered the United States. Max can't help but feel frustrated, knowing that Lucy continues to abduct Amy, forcing the team into repeated rescue missions. When Amy is captured again, Max steps up to take command and leads the charge to Lucy’s hideout nestled within a dockside warehouse.
With a mix of determination, wit, and subtle chaos, Max, Janet, and the perpetually smoking Dominique confront Lucy and her henchmen, led by the loyal Billy Skids. In a twist unbeknownst to the D.E.B.S. or Lucy's crew, Amy and Lucy share a secret romantic relationship. Each capture is a guise for their passionate rendezvous, with Amy cleverly timing her “rescues.” However, Lucy grows weary of their repetitive routine.
During an intimate moment, Amy professes her love for Lucy, much to her joy. Meanwhile, Max, Janet, and Dominique engage in an action-packed showdown, with Dominique never once letting go of her cigarette. The trio eventually finds themselves at Lucy's private quarters, hearing what they presume to be Amy in distress. However, unbeknownst to them, Amy's cries are not out of pain but ecstasy as she reaches a passionate climax with Lucy.
In a rush, Lucy and Amy dress, discussing the upcoming D.E.B.S. mission in Uganda. Just as Amy signals for Lucy to play her part in their charade, Lucy knocks her out and escapes, leaving Max, Janet, and Dominique oblivious to the underlying truth of Amy’s secret affair with their nemesis. Grateful for their intervention, Amy thanks her teammates once more as they exit the warehouse and step into the waning evening light. Janet, however, is keen to know if Amy has stained her treasured sweater amidst their latest adventure.
