In 2015, Sonar Entertainment optioned the screen rights to Stephen King's novel Mr. Mercedes with the intent of developing it into a limited series, with David E. Kelley writing and Jack Bender directing.

The second season expanded the adaptation to draw on all three novels of King's Bill Hodges trilogy: Mr. Mercedes, Finders Keepers, and End of Watch.

Anton Yelchin was originally cast in one of the series' two lead roles, but following his death in June 2016, the role was recast with Harry Treadaway stepping in as Brady Hartsfield.

Ann-Margret was initially cast in a role for the series, but she was recast with Holland Taylor after Ann-Margret withdrew due to an illness in her family.

Stephen King himself made a cameo appearance in the series, as reported in April 2017.

Principal photography for the first season began in February 2017 in Charleston, South Carolina, including filming in the Wagener Terrace neighborhood and at the Little Jack's Tavern restaurant on Upper King Street.

During filming on March 2, 2019, special effects technician Mike Wilks survived a near-electrocution incident on set.

The character Holly Gibney, introduced in the Bill Hodges trilogy, later became a main character in King's 2018 novel The Outsider, which was adapted into an HBO miniseries with Cynthia Erivo playing the role.