The Batman legend takes an unexpected turn when the Caped Crusader vanishes from the crime-ridden city of New Gotham and his legacy is taken over by a trio of beautiful and relentless heroines - the Birds of Prey. Barbara Gordon started out as Batman's protege, Batgirl, but an attack by The Joker left her confined to a wheelchair. Reinventing herself as Oracle, she takes under her wing Helena Kyle, the secret daughter of Batman and Catwoman, who quickly grows into the fierce and beautiful "Huntress", and Dinah, a teenage runaway who is drawn to the city by meta-human visions. With the help of the only honest cop in New Gotham, Detective Jesse Reese, the Birds of Prey fight their first battle against a mysterious madwoman who is bent on their destruction.

Slick, an evil meta-human who can turn from solid to liquid, is hired by Dr. Quinzel to kill the honest cops who stand in her way. When Reese is the next intended victim, Helena comes to his aid and their mutual attraction continues to grow. Meanwhile, Barbara believes Dinah's story that she's just a runaway, but Helena remains suspicious.

Helena and Detective Reese clash again when they both try to track down a serial killer who destroys metahumans by taking on their powers. Meanwhile, Dinah ditches school when she learns from Helena there is a metahuman-only bar, and Barbara meets Wade's parents who think she is not normal enough for their son.

When Helena rescues an abandoned baby boy and brings him back to the Clocktower, Barbara and Dinah try to help, but to everyone's surprise, the baby, Guy, is only happy when Helena is holding him. Even more surprising is the fact that Guy wakes up from his nap as a walking, talking 5-year-old and is soon a teenager. Now in a race against time, the Birds of Prey discover that Guy is programmed to live his entire life in three days, and to kill the first person he attaches to, putting Helena in grave danger.

At the request of Det. Reese, Helena goes undercover to help bring down a gang of thieves terrorizing New Gotham and quickly discovers that the gang is part of a larger infrastructure. Helena goes after the big boss until her cover is blown, putting her in grave danger. Meanwhile, Barbara has to deal with her fear of intimacy when her relationship with Wade takes a serious turn.

Already frustrated with her difficult relationship with Reese, Helena is intrigued when she meets Darkstrike, a metahuman who has come to New Gotham on the trail of a serial killer. Meanwhile, Barbara and Dinah discover that Darkstrike has a dangerous alter ego.

Helena is thrilled when her best friend from high school, Sandra, returns to New Gotham, but the Birds are troubled by a series of murders with the unmistakable mark of Batgirl's nemesis, Lady Shiva. Determined to fight Lady Shiva as an equal, Barbara dusts off her Batgirl costume and experiments with technology that allows her to leave the wheelchair.

When a hit is put out on the life of legendary mob boss, Al Hawke, the only person he trusts to protect him is his son, Detective Reese. Reese turns to Helena for help, but when she learns that Reese's father is the same man who killed Dinah's mother, Black Canary, her loyalties are tested.

When young metahuman women are abducted in New Gotham, Helena's investigation leads her to uncover a secret club where the captive women are drugged and forced to fight each other in an arena. When Helena is also abducted, it is up to Dinah to rescue her.

When Helena's former classmates descend upon New Gotham for their fifth class reunion, two of the alums are brutally murdered. While Helena tries to find the killer, she fears that Reese's investigation will lead him to learn too much about her true identity.

Citizens of New Gotham are being turned into clay by a villain whose crimes are similar to those of Clayface, the master of shape-shifting who has been in Arkham Asylum for many years. Helena confronts Clayface and learns that his son, Chris, is responsible for the new rash of crimes. She also finds out who was responsible for her mother's murder.

Harley Quinn acquires the power to hypnotize others with her eyes, and persuades Helena to reveal the secrets of the Clocktower, along with Barbara's and Dinah's true identities. She soon has all the ammunition she needs to wreak havoc on The Birds as well as the rest of New Gotham.