The campaign that became Critical Role started two years before the show as a one-off, simplified Dungeons & Dragons 4th edition game organized for Liam O'Brien's birthday, while O'Brien was serving as Matthew Mercer's voice director on Resident Evil 6.

The home game initially used the Pathfinder ruleset before being converted to Dungeons & Dragons 5th edition to streamline gameplay before the web series began airing in March 2015.

Felicia Day approached the group about live-streaming their private home game for Geek & Sundry after hearing about it from Ashley Johnson; the initial pitch would have had players switch to a video game to resolve combat, but Matthew Mercer insisted on keeping tabletop play.

There were originally eight cast member players in the home game; Orion Acaba left the show after episode 27 of campaign one, and his character Tiberius later appeared in the first seven issues of the prequel comic Critical Role: Vox Machina Origins.

The term 'Critters' for fans of the show was suggested by Liam O'Brien during the Q&A session at the end of episode 10 of campaign one.

The show's first professional set at Geek & Sundry, nicknamed 'Felicia's Bedroom', separated the cast onto three tables and had poor audio, cameras blocking eyelines, and long distances that made it hard for players to see the battle maps; Liam O'Brien said it felt like 'a child's diorama for a school project'.

A custom game table designed by Wyrmwood, allowing the cast to sit together while being filmed from multiple angles, was added to the set in July 2017.

The show switched from live broadcasting to pre-recording starting with campaign two episode 100, due to filming conditions during the COVID-19 pandemic.

The Kickstarter campaign launched in March 2019 to fund a 22-minute animated special turned into a fully funded 10-episode animated series after raising $11.3 million, making it one of the most quickly funded and most funded Kickstarter campaigns for TV and film projects in the platform's history.

A 2021 leak of Twitch data revealed Critical Role was among the platform's highest earners, receiving a total direct payout of $9,626,712 between September 2019 and September 2021 in gross income from subscriptions and ad revenue.

Sam Riegel took a leave of absence from campaign three in 2024 to receive cancer treatment after his character FCG sacrificed themselves in episode 91, later returning to the show with a new character in June 2024.

Campaign three's finale, airing February 6, 2025, was the longest episode of the series at over eight and a half hours, and the show had gone on an unplanned hiatus in January 2025 due to California wildfires affecting the studio, cast, and crew in the Los Angeles area.