The film stars Kiera Allen as disabled teenager Chloe Sherman, who begins to suspect that her mother, Diane (Sarah Paulson), has been keeping a dark secret about her upbringing.

A woman named Diane Sherman gives birth to a premature baby, whom she goes to see lying in an incubator, surrounded by the hospital staff.

One morning, while looking through a bag of groceries for chocolate, Chloe finds a prescription bottle of green pills with Diane's name on the label.

The pharmacist at the desk reveals the green pills are actually a relaxant called Ridocaine, which had been only approved for dogs and, if they were being taken by a human, it could paralyze their legs.

She is forced to throw her wheelchair down the stairs and accidentally falls, sustaining minor injuries but also discovering that she can move one of her toes, due to having not taken Ridocaine in the last few days.

Outside down the road, Chloe sees a mail truck and rushes to stop it; she explains her situation to Tom, the postal worker, who agrees to help her.

While closing up the van to take Chloe to the police station, Diane suddenly appears and stabs Tom in the neck with a syringe.

When she awakens, she is in the basement of her house, with her wheelchair chained to a steel pole as Diane drags Tom's body through her hallway.

Armed with a handgun, Diane then sneaks in and ties Chloe to a wheelchair to escape; the nurse finds the bed empty and alerts hospital security.

She takes out three plastic-wrapped Ridocaine pills that were concealed under her tongue, and tells Diane that she still loves her before asking her to open her mouth wide.

In June 2018, it was announced Lionsgate would produce, distribute, and finance the film, with Aneesh Chaganty directing, from a screenplay he wrote alongside Sev Ohanian.

The site's critics consensus reads, "Solid acting and expertly ratcheted tension help Run transcend its familiar trappings to deliver a delightfully suspenseful thriller.

"[21] Ryan Lattanzio of IndieWire gave the film a "C+" and said, "There's enough go-for-broke and whiplash-inducing shifts in tone on display to suggest this filmmaking duo has a future, even when their characters don't seem to have a past.

[23] In November 2018, Ohanian revealed that Run includes intentional references to his previous film Searching, while also stating that the latter has connections to the prior as well.

[24] Later in November 2020, Chaganty and Ohanian revealed that one of these connections involves a brief appearance by the character of Hannah Pardy from Searching as a stock photo model.