Madame Web

In 1973, in the Peruvian Amazon, Constance Webb (Kerry Bishé) and her coworker Ezekiel Sims (Tahar Rahim) are researching a rare spider. Despite being pregnant and feeling weak, Constance perseveres. When they finally locate the spider, Sims betrays the team, killing everyone. Constance struggles to seize the spider from him, but Sims shoots her and leaves her for dead.

From the trees, a hidden tribe called Las Arañas ("The Spiders") emerges and rescues Constance, taking her to their secret cave. They submerge her in a pool and use the rare spider to bite her just before she gives birth to her daughter. As she dies, Constance sees her baby and is told by the Arañas chief that the girl is destined for greatness.

In 2003, in Queens, the girl, now grown up, is Cassandra "Cassie" Webb (Dakota Johnson). She works as a paramedic alongside Ben Parker (Adam Scott; yes, Uncle Ben). After responding to an emergency, Cassie and Ben return to the hospital. The son of her patient gives her a drawing to thank her for helping his mom, but Cassie feels awkward until Ben encourages her to accept it.

Sims now lives in New York, tormented by recurring nightmares in which three young women with spider powers attack and kill him. He confides in an undercover NSA agent he sleeps with, but when he discovers her true identity, he uses his spider-given powers to poison her.

Cassie and Ben respond to an emergency involving a car teetering over a bridge. They manage to rescue the driver, but Cassie becomes trapped in the vehicle as it plunges into the river. While underwater, a powerful force envelops her, seemingly activating something within her. She experiences visions and sounds before Ben revives her.

Later, Cassie attends a baby shower for Ben's sister-in-law, Mary (Emma Roberts). During the games, Cassie awkwardly mentions her mother's death during childbirth, making Mary uncomfortable. She also experiences a strange sense of déjà vu, feeling as though she has already witnessed a moment at the party.

A fire breaks out in a nearby building, prompting Cassie and Ben to respond. While tending to an injured man, Cassie has a vision of herself over the body of her coworker O'Neill (Mike Epps), with his blood on her hands. Snapping back to the present, she realizes something bad is about to happen and urges O'Neill to let her drive the ambulance. He dismisses her concerns and drives off, only to be fatally struck by a truck moments later.

Devastated, Cassie returns home, fearing she cannot control her visions. She then has another premonition of a bird flying into her window, breaking it and dying upon impact. Recognizing it as a vision, she leaves the window open, allowing the bird to fly in and out safely, which reassures her that she can influence future events.

Sims, with the help of his assistant Amaria (Zosia Mamet), uses face-scanning technology to identify his potential killers. They focus on three teenagers: Julia Cornwall (Sydney Sweeney), Anya Corazon (Isabela Merced), and Martha “Mattie” Franklin (Celeste O'Connor). Meanwhile, Cassie boards a train just as the three girls are also boarding. She has a vision of Sims killing them and quickly ushers them off the train. The girls initially believe Cassie is attempting to kidnap them until they see Sims, dressed in a black Spider-Man-like suit, crawling on the ceiling and killing police officers.

Cassie commandeers a cab and convinces the girls to join her. After escaping Sims, they exchange awkward introductions. Cassie takes them to the woods to explain her visions. The girls realize they have connections to Cassie: Julia is the stepdaughter of Cassie's patient (the one whose son gave her the drawing), Anya recognizes Cassie as a resident in her building who leaves junk mail everywhere, and Mattie recalls flipping Cassie off when she almost hit her with the ambulance while skateboarding. Cassie leaves the girls in the woods to keep them safe from Sims while she investigates further.

Returning to her apartment, Cassie discovers pictures and journals belonging to her mother, Constance, including a photo of Constance with Sims. Meanwhile, the girls, bored and restless, decide to go to a nearby diner for food before Cassie returns. Julia and Anya join Mattie, and they start hanging out with some boys they meet there.

Cassie returns to the woods only to find the girls missing. She has a vision of them at a diner where Julia and Mattie are killed before Sims takes her out. Panicked, she rushes to the diner, but Sims gets there first. Before he can reach the girls, Cassie crashes through the diner's front, plowing into Sims. The girls run to the car, and they flee together, with Cassie scolding them for not listening to her. Meanwhile, Sims learns from Amaria that Cassie is Constance's daughter.

Cassie takes the girls to a motel to hide them properly. The girls explain their difficult situations: Julia's mother is in a psych ward, and her father remarried to a woman who doesn't want her around. Anya's mother died when she was young, and her father was deported while she was at school, leaving her fearful of the same fate. Mattie's father is a wealthy but corrupt politician, and she wants nothing to do with him. Determined to stop Sims, Cassie decides to investigate further, leaving the girls with Ben.

Cassie returns to the diner and experiences a psychic connection to Sims. Aware of her powers, Sims explains why he is hunting the girls, but Cassie insists there's no way they could be capable of killing him.

Cassie travels to Peru and visits the site where Constance had been working. She meets the chief of Las Arañas, who takes her to the cave where she was born. There, he separates her spirit from her physical form, allowing her to witness visions of her mother during her pregnancy. Contrary to what Cassie had believed, she sees that Constance was dedicated to ensuring Cassie's healthy birth, even while researching ways to prevent her from contracting a fatal disease. Cassie returns to her body and begins her journey back home.

Meanwhile, in New York, Mary goes into labor, and Ben rushes all the women to the hospital. Amaria scans the girls, alerting Sims, who starts heading their way. Cassie arrives home to find it empty and has a vision of Sims killing everyone downtown. She steals an ambulance and races to save them. Sims catches up to the group and nearly detonates a grenade, but Cassie crashes through a billboard into Sims, retrieves the girls, and leaves Ben and Mary to continue to the hospital.

Cassie has the girls assist her in evading Sims as she speeds through the streets, but the ambulance eventually dies. They reach a warehouse where Cassie radios for a chopper to extract them. She instructs the girls to set off flares in explosive crates in preparation for Sims' arrival. As Sims enters, the explosives go off, and the girls rush to the rooftop. Despite their efforts to climb higher, Sims manages to bring down the chopper. The girls attempt to help Cassie, but they all end up hanging precariously over the edge. Sims taunts Cassie, claiming she can't save them all. Drawing on her experience with Las Arañas, Cassie astral-projects herself to save each girl and then leads Sims into a trap. The warehouse's sign begins to collapse, trapping Sims under the debris. Cassie reveals that his visions were not warnings about the girls, but about her. Sims falls and is crushed by a collapsing Pepsi sign. Cassie also falls into the river, and a firework blinds her as it flies into her face. Julia jumps in to save Cassie, while Anya and Mattie perform CPR as Cassie taught them, reviving her.

At the hospital, the girls gather around Cassie's bedside, grateful for their lives and each other. Meanwhile, Mary gives birth to a healthy baby boy, hinting at his future as a famous web-slinger.

Left blind and paralyzed below the waist, Cassie welcomes Julia, Anya, and Mattie into her apartment. She shares a vision she had, envisioning the four of them as superpowered crime fighters donning their suits. Despite her challenges, Cassie smiles, anticipating the adventures that lie ahead.