In a bustling nightclub, a notorious drug dealer relishes a night out in the company of multiple women. Suddenly, one of his jaded henchmen informs him that he has brought along a young lady eager for drugs, claiming he’s driving the dealer's car. Initially furious, the dealer's mood shifts upon seeing the stunning woman. However, the encounter takes a deadly turn as she returns with him to a run-down apartment. Just when intimacy seems likely, she reveals a sawed-off shotgun hidden in her macrame purse and blasts his head off.
In another room, the henchman is lost in a drug high when the woman confronts him, introducing herself as Coffin, and disclosing that her sister, LuBelle Coffin, is now in a hospital due to tainted heroin, leaving her mentally impaired. In a moment of retribution, she forces the henchman to take another hit, which ultimately leads to his demise.
The woman, known to her friends and allies as Coffy (Pam Grier), serves as a nurse by day but seeks vengeance for her sister. She is romantically involved with Howard Brunswick (Booker Bradshaw), a political hopeful. Coffy soon learns from her friend Carter (William Elliott), a straight-laced cop refusing dirty money from the mobster Arturo Vitroni (Allan Arbus), that things are about to get much more dangerous as Vitroni's men beat him up for his defiance.
Fueled by anger and determination, Coffy sets out to take down the local druglords. She soon discovers the involvement of King George (Robert DoQui), a notorious pusher who is also a prominent pimp. Coffy remembers Priscilla, a former prostitute who was once treated at the hospital where she worked, and visits her for intel about George's operations. Priscilla informs her about Vitroni, who has a penchant for brutalizing his women, but hesitates to disclose the location of George's stash due to fear for her life. When Priscilla threatens Coffy with a knife, Coffy retaliates in rage, revealing her determination. Priscilla reluctantly reveals that George keeps his drugs hidden under the fireplace.
Armed with this information, Coffy poses as a Jamaican hooker named Mystique to infiltrate King George's realm. At a wild party hosted by George, Coffy cleverly disposes of his heroin stash, replacing it with sugar. This sparks jealousy in George's girlfriend, Meg (Linda Haynes), who confronts Coffy. In the ensuing chaotic confrontation, Coffy uses hidden razor blades in her hair to fend off Meg, impressing Vitroni, who becomes smitten.
Coffy attempts to execute her plan against Vitroni, but is captured by Omar (Sid Haig), Vitroni's bodyguard. They mistake her for a hitwoman sent by King George, leading them to retaliate. As they plot George's demise, they keep Coffy captive. Her cover is blown, leading to a tangled web of betrayals when Howard is summoned to clear up the situation. Despite Coffy's pleas that Howard had no involvement, he chooses to save himself, ultimately leaving her to face a grim fate.
Taking matters into her own hands, Coffy cunningly escapes with a knife against Omar and dispatches several henchmen, one of whom meets a violent end on a busy freeway. After stealing a getaway car, she leads a furious path back to Vitroni's stronghold, blasting through the house with her shotgun, exacting vengeance on all those responsible for her suffering and her sister's fate.
Coffy's final act of revenge is to confront Howard when she finds him at his beach house. With her shotgun drawn, she reveals her survival and the bloody trail she left behind. Just as Howard attempts to justify his actions, a half-naked woman calls out to him from upstairs, prompting Coffy to shoot him without hesitation, revealing the extent of her isolation and rage. She steps out into the morning light, weary but resolute, a survivor stained by blood yet surviving in a world of darkness.
