Mark Wahlberg's character stated, "People sleep peaceably in their beds at night only because rough men stand ready to do violence on their behalf." The quote is attributable to English author George Orwell.

The script was written with Mark Wahlberg in mind.

On February 5, 2018, Colombian President Juan Manuel Santos showed up during filming in one of the locations in Colombia. Director Peter Berg even had President Santos try to shoot one of the action sequence of the film.

On March 28, 2017 at CinemaCon, Mark Wahlberg and director Peter Berg announced that they were planning Mile 22 (2018) to become a trilogy, describing "an action franchise at STX Entertainment."

Mark Wahlberg worked with director Peter Berg in Lone Survivor (2013), Deepwater Horizon (2016), Patriots Day (2016) and Mile 22 (2018).

This was the second occasion where Mark Wahlberg and John Malkovich worked together and the second occasion where John Malkovich worked with Peter Berg. The last time where all three worked together was on Deepwater Horizon (2016).

This was the Hollywood feature film debut for South Korean singer Chae-rin Lee, who goes by the stage name "CL."

The movie was filmed on location in Bogota, Colombia.

Principal photography was shot in Atlanta, Georgia in November and December 2017 under the working title "Ground Branch."

On November 7, 2017, Lauren Cohan was cast in the film.

On July 2, 2015, Mark Wahlberg was cast in the film to play the male lead role, while Peter Berg was also confirmed to direct the film for STX Entertainment.

The film was originally going to be released on August 3, 2018, but it was pushed back two weeks from its original release date of August 3, 2018 to August 17, 2018.