In April 2015, Paramount Television announced it would adapt Caleb Carr's 1994 novel The Alienist as an event television series in partnership with Anonymous Content, with Eric Roth as executive producer and Hossein Amini as writer and executive producer.

Cary Fukunaga was originally set to direct all episodes of the series and serve as executive producer, but he was replaced as director by Jakob Verbruggen in September 2016 due to scheduling conflicts, though Fukunaga remained on board as an executive producer.

Writer-director John Sayles joined the series as a writer in July 2015, and novelist Caleb Carr himself came aboard as a consulting producer later that same month.

In May 2015, TNT made a deal to produce the series at a cost of $5 million per episode.

Daniel Brühl and Luke Evans were cast as Dr. Laszlo Kreizler and John Moore in November 2016, followed by Dakota Fanning as Sara Howard in January 2017, with the rest of the main cast rounded out through early 2017.

The character of Sara Howard is loosely based on the real story of Isabella Goodwin, who became New York's first female detective.

On its release, the first season received an approval rating of 67% on Rotten Tomatoes with critics praising its cast and production design but criticizing its slow pace, while the second season, Angel of Darkness, scored higher at 81% approval.

After TNT ordered a sequel series in August 2018 based on Carr's 1997 follow-up novel The Angel of Darkness, the second season premiered in July 2020 as The Alienist: Angel of Darkness, with Netflix acquiring international rights to the show.