Emily Blunt was originally attached to reprise her role in Sicario (2015) as FBI Agent Kate Macer. However, once director Stefano Sollima was attached to the film, he ultimately decided not to use Blunt or her character in the film, noting that Macer represented the moral compass in Sicario (2015), whereas he did not want any character to serve as moral guidance in the sequel. Screenwriter Taylor Sheridan, who wrote the story and screenplay for both films, also stated in interviews that he could not think of a reason to keep Agent Macer in the second film, and that her character's story had already come full circle in the first installment.
The film is dedicated to the memory of Jóhann Jóhannsson, the composer of the first film, who died in February 2018.
Denis Villeneuve could not return to direct this sequel due to scheduling conflicts with Arrival (2016) and Blade Runner 2049 (2017). Early in development, he was going to direct the film before committing to Arrival and Blade Runner, which conflicted with the making of this film.
The film was announced less than a month after the release of the first instalment.