The song was released as the title track and lead single from their fifth studio album Fear Inoculum.
[3] Upon its debut on the Billboard Hot 100, "Fear Inoculum" broke the Guinness World Record for the longest song ever to chart on the Hot 100, overtaking David Bowie's "Blackstar", until André 3000 broke the record again in 2023 with "I Swear, I Really Wanted to Make a 'Rap' Album but This Is Literally the Way the Wind Blew Me This Time".
[4][5] Loudwire described the song as having "Middle Eastern drum patterns" and called it a "slow burn building to big, cathartic crescendos".
They also praised Keenan's vocals, noting the lyrics "seem to address a rejection of fear and negativity from outside sources.
[9][10][11] It debuted on the Billboard Top Rock Songs chart at number 4 on the August 17 release.