In August 2017, Stephen King said Lisey's Story was his favorite of his novels and expressed hope to see it adapted as a TV series, noting that a two-hour film would suffer from what he called 'sitting on a suitcase syndrome' where too much material has to be crammed in, whereas a 10-hour TV format would give it room to breathe.

In April 2019, Apple Inc. acquired the rights to the novel and gave it a straight-to-series order of eight episodes, with all episodes personally scripted by Stephen King himself and produced by J. J. Abrams' Bad Robot Productions.

Director Pablo Larraín worked with production designer Guy Hendrix Dyas to craft a unique visual style blending the real world with the novel's fantastical elements, including designing 'The Long Boy,' a terrifying creature that exemplifies the series' merging of horror and surrealism.

Filming began in October 2019 at the historic Van Liew-Suydam House in Franklin Township, Somerset County, New Jersey, before moving to the village of Tuckahoe in Westchester County, New York in December 2019.

Production was shut down in mid-March 2020 due to the COVID-19 pandemic, with only a few weeks of shooting reportedly remaining at the time; Julianne Moore confirmed her filming was finally completed in September 2020.

Director Pablo Larraín chose British electronic musician Clark to score the series after hearing his soundtrack for Daniel Isn't Real (2019), contacting him directly; Larraín wanted emotionally driven character themes rather than purely functional background music.

The score was recorded with a 30-piece string ensemble at AIR Studios and a 30-piece choir at Abbey Road Studios, with violinist Rakhi Singh performing the main title theme; the choir also used percussive vocal techniques to create the creature 'The Long Boy''s voice, which Larraín wanted to sound 'believably human' rather than theatrical.

The miniseries received mixed reviews, holding a 53% approval rating on Rotten Tomatoes and a Metascore of 49/100, with critics praising Julianne Moore's performance but criticizing an overreliance on the source material and a sluggish pace.