Pantheon is based on Ken Liu's short stories 'The Gods Will Not Be Chained', 'The Gods Will Not Be Slain', 'The Gods Have Not Died in Vain', 'Staying Behind', 'Altogether Elsewhere, Vast Herds of Reindeer' and 'Seven Birthdays', all from his collection The Hidden Girl and Other Stories.

AMC opened a writers room for the animated drama in August 2018, and in March 2020 gave it a two-season order of eight episodes each; it was AMC's first hour-long animated drama original series.

Despite the two-season order, AMC canceled the series after one season on January 8, 2023, and pulled it from AMC+ and HIDIVE, before Amazon Prime Video picked it up for release in September 2023 and Netflix later acquired it for international distribution.

The character Stephen Holstrom, the visionary founder of Logorhythms, is modelled after real-life tech figures Ray Kurzweil and Steve Jobs.

The score by Marco Beltrami, Brandon Roberts, and Buck Sanders was never officially released by the studio; Buck Sanders began releasing it independently on YouTube starting in February 2025.

Ken Liu, a former Microsoft software engineer, took part in the early stages of story development specifically to help devise scientifically sound ideas, while Stanley Von Medvey was brought on as assistant director and visual development supervisor to give the show a hard sci-fi visual standard.

A plot point showing that uploaded intelligences become more productive when their brain's emotional centers are reintegrated is based on a real study of master chess players, which found emotion and intuition play as significant a role as pure calculation.

The series deliberately avoids technobabble in favor of real technical jargon, with characters discussing genuine computer science concepts such as Edsger Dijkstra's dining philosophers problem.