The series is a reboot of the 2004 television series The 4400, first announced in development at the CW on November 7, 2018, with Taylor Elmore and Craig Sweeney originally attached to write and produce the pilot.

The project was delayed and moved to the next development cycle in February 2019 because the scripts were not ready in time, before being redeveloped for the 2020–21 season under new writer Ariana Jackson, who received a straight-to-series order in February 2021.

Patrick John Flueger, who starred in the original 2004 series, returned to guest star in the twelfth episode of the reboot.

Scott Peters, co-creator of the original 2004 series, directed the twelfth episode of the reboot.

Principal photography took place in Chicago, with filming on the first episode beginning June 7, 2021, and the rest of the series shooting from July 26 to December 7, 2021.

The CW canceled 4400 after just one season on May 12, 2022, as part of a mass cancellation wave that included six other shows the same day, an event some fans nicknamed 'the Red Wedding' after Game of Thrones.

The wave of cancellations disproportionately affected shows with Black leads or predominantly Black casts, including 4400, Naomi, Batwoman, Charmed, and Tom Swift.

The series received an 82% approval rating on Rotten Tomatoes and was nominated for Outstanding New TV Series at the 33rd GLAAD Media Awards in 2022.